Immunomodulatory Treatment Versus Systemic Steroids in Inflammatory Choroidal Neovascularization Secondary to Idiopathic Multifocal Choroiditis.

PURPOSE: To evaluate the influence of immunomodulatory therapy (IMT) on visual and treatment outcomes of inflammatory choroidal neovascularization (iCNV) in patients affected by multifocal choroiditis (MFC), and to compare them to patients treated with steroids as needed. DESIGN: Multicenter retrospective matched cohort study. METHODS: Patients affected by MFC with iCNV were divided into a IMT group and a "steroids as needed" group and matched according to the time between diagnosis and beginning of systemic treatment. Visual acuity (VA), number of anti-vascular endothelial growth factor (VEGF) intravitreal injections, and number of iCNV reactivations during 2 years of follow-up after treatment initiation were compared between the 2 groups. RESULTS: A total of 66 eyes of 58 patients were included, equally divided into the 2 groups. Patients in the IMT group had a lower relative risk (RR) of iCNV reactivation (0.64, P = .04) and of anti-VEGF intravitreal injection retreatment (0.59, P = .02). Relapses of MFC-related inflammation were independently associated with a higher RRs of iCNV reactivation (1.22, P = .003). Final VA was higher in the IMT compared to the steroids as needed group (mean [SD], 69.1 [15.1] vs 77.1 [8.9] letters, P = .01), and IMT was associated with greater VA gains over time (+2.5 letters per year, P = .04). CONCLUSIONS: IMT was associated with better visual and treatment outcomes in MFC complicated by iCNV compared to steroids as needed. The better outcomes of the IMT group and the association between MFC-related inflammation and iCNV reactivations highlight the need for tighter control of inflammation to prevent iCNV relapses and visual loss.

The multimodal imaging features and outcomes of multifocal choroiditis/punctate inner choroidopathy lesion with multiple evanescent white dot syndrome-like features: a retrospective study.

BACKGROUND: Multiple evanescent white dot syndrome (MEWDS)-like features is a rare condition triggered by a macular disease or iatrogenic injury, exhibiting MEWDS changes in the fundus. This study aims to describe the multimodal imaging features and outcomes of multifocal choroiditis/punctate inner choroidopathy (MFC/PIC) lesions with MEWDS-like features. METHODS: Six cases were studied retrospectively. All cases were given regional and oral corticosteroids. RESULTS: All cases showed an isolated juxtafoveal yellowish-white MFC/PIC lesion with disruption of RPE-Bruch's membrane-choriocapillaris complex (RPE-BM-CC), subretinal hyperreflective materials and choroidal thickening on optical coherence tomography. Two weeks after presentation, the grayish-white dots disappeared spontaneously and the corticosteroids were given. After four weeks, the ellipsoid zone (EZ) around the lesion and hyper-autofluorescence resolved. After 13 weeks, five cases showed shrinkage of the juxtafoveal lesion and restoration of foveal EZ. After six months, the juxtafoveal lesion became pigmented. Only one case developed type 2 choroidal neovascularization. CONCLUSIONS: The clinical course of MEWDS-like manifestations is still evanescent in our cases. The yellowish-white juxtafoveal MFC/PIC lesions with disruption of RPE-BM-CC and choroidal thickening showed a well-controlled prognosis after corticosteroid treatment.

Association of Risk Variants in the CFH Gene With Elevated Levels of Coagulation and Complement Factors in Idiopathic Multifocal Choroiditis.

Importance: Idiopathic multifocal choroiditis (MFC) is poorly understood, thereby hindering optimal treatment and monitoring of patients. Objective: To identify the genes and pathways associated with idiopathic MFC. Design, Setting, and Participants: This was a case-control genome-wide association study (GWAS) and protein study of blood plasma samples conducted from March 2006 to February 2022. This was a multicenter study involving 6 Dutch universities. Participants were grouped into 2 cohorts: cohort 1 consisted of Dutch patients with idiopathic MFC and controls, and cohort 2 consisted of patients with MFC and controls. Plasma samples from patients with idiopathic MFC who had not received treatment were subjected to targeted proteomics. Idiopathic MFC was diagnosed according to the Standardization of Uveitis Nomenclature (SUN) Working Group guidelines for punctate inner choroidopathy and multifocal choroiditis with panuveitis. Data were analyzed from July 2021 to October 2022. Main outcomes and measures: Genetic variants associated with idiopathic MFC and risk variants associated with plasma protein concentrations in patients. Results: This study included a total of 4437 participants in cohort 1 (170 [3.8%] Dutch patients with idiopathic MFC and 4267 [96.2%] controls; mean [SD] age, 55 [18] years; 2443 female [55%]) and 1344 participants in cohort 2 (52 [3.9%] patients with MFC and 1292 [96.1%] controls; 737 male [55%]). The primary GWAS association mapped to the CFH gene with genome-wide significance (lead variant the A allele of rs7535263; odds ratio [OR], 0.52; 95% CI, 0.41-0.64; P = 9.3 × 10-9). There was no genome-wide significant association with classical human leukocyte antigen (HLA) alleles (lead classical allele, HLA-A*31:01; P = .002). The association with rs7535263 showed consistent direction of effect in an independent cohort of 52 cases and 1292 control samples (combined meta-analysis OR, 0.58; 95% CI, 0.38-0.77; P = 3.0 × 10-8). In proteomic analysis of 87 patients, the risk allele G of rs7535263 in the CFH gene was strongly associated with increased plasma concentrations of factor H-related (FHR) proteins (eg, FHR-2, likelihood ratio test, adjusted P = 1.1 × 10-3) and proteins involved in platelet activation and the complement cascade. Conclusions and relevance: Results suggest that CFH gene variants increase systemic concentrations of key factors of the complement and coagulation cascades, thereby conferring susceptibility to idiopathic MFC. These findings suggest that the complement and coagulation pathways may be key targets for the treatment of idiopathic MFC.

THE CHRYSANTHEMUM PHENOTYPE OF IDIOPATHIC MULTIFOCAL CHOROIDITIS.

PURPOSE: To describe the clinical characteristics and multimodal imaging features of a distinctive subtype of active idiopathic multifocal choroiditis (iMFC) lesions with grey-yellow chorioretinal lesions surrounded by smaller satellite dots, a presentation referred to as "chrysanthemum lesions." METHODS: Retrospective, observational, multicenter case series of eyes with active iMFC and chrysanthemum lesions. Multimodal imaging features were reviewed and presented. RESULTS: Twenty-five eyes from 20 patients (12 women and 8 men), with a mean age of 35.8 ± 17.0 years (range, 7-78 years) were included. Chrysanthemum lesions were equally located in the macula (48.0%) or the mid/far periphery (52.0%). The number of lesions per eye varied from 1 (16.0%) to more than 20 (56.0%). On optical coherence tomography, chrysanthemum lesions showed typical features of iMFC, including subretinal hyperreflective material splitting the retinal pigment epithelium/Bruch membrane. Chrysanthemum lesions were hypoautofluorescent on fundus autofluorescence imaging, hyperfluorescent on fluorescein angiography, hypofluorescent on indocyanine green angiography, and associated with choriocapillaris flow signal deficit on optical coherence tomography angiography. CONCLUSION: Active iMFC may present with findings resembling chrysanthemum lesions. The distinctive lesion morphology on ophthalmoscopic examination, the large number of lesions, and the high prevalence of exclusive midperipheral and far peripheral involvement may represent a distinctive phenotype of iMFC.

PRIMARY MULTIPLE EVANESCENT WHITE DOT SYNDROME AND MULTIPLE EVANESCENT WHITE DOT SYNDROME SECONDARY TO MULTIFOCAL CHOROIDITIS/PUNCTATE INNER CHOROIDOPATHY: A Comparative Study.

PURPOSE: To present and compare the clinical features and multimodal imaging (MMI) findings of the primary form of multiple evanescent white dot syndrome (MEWDS) and MEWDS secondary to multifocal choroiditis/punctate inner choroidopathy (MFC/PIC). METHODS: A prospective case series. Thirty eyes of 30 MEWDS patients were included and divided into the primary MEWDS group and MEWDS secondary to MFC/PIC group. Demographic, epidemiologic, and clinical characteristics and MEWDS-related MMI findings of the two groups were compared. RESULTS: Seventeen eyes from 17 patients with primary MEWDS and 13 eyes from 13 patients with MEWDS secondary to MFC/PIC were evaluated. Patients with MEWDS secondary to MFC/PIC tended to have a higher degree of myopia than those with primary MEWDS. No other significant differences in demographic, epidemiologic, and clinical characteristics and MMI findings were found between the two groups. CONCLUSION: "MEWDS-like reaction" hypothesis seems to be correct for MEWDS secondary to MFC/PIC, and the authors highlight the importance of MMI examinations in MEWDS. Further research is needed to confirm whether the hypothesis is applicable to other forms of secondary MEWDS.

Exploring Imaging Characteristics Associated With Disease Activity in Idiopathic Multifocal Choroiditis: A Multimodal Imaging Approach.

PURPOSE: To identify characteristics on multimodal imaging (MMI) in idiopathic multifocal choroiditis (MFC) that can identify inflammatory activity and distinguish choroidal neovascularization (CNV) activity from inflammatory activity. DESIGN: Prospective cohort study. METHODS: MMI consisted of spectral-domain optical coherence tomography (angiography) (SD-OCT(A)), fundus autofluorescence, fundus photography, infrared imaging, fluorescein angiography (FA), and indocyanine green angiography (ICGA). MMI characteristics obtained during active and inactive disease were compared within the same lesion. Secondly, MMI characteristics were compared between active inflammatory lesions with and without CNV activity. RESULTS: Fifty patients (110 lesions) were included. In 96 lesions without CNV activity, the mean focal choroidal thickness was increased during the active disease (205 µm) compared to the inactive disease (180 µm) (P ≤ .001). Lesions with inflammatory activity typically demonstrated moderately reflective material located in the sub-retinal pigment epithelium (RPE) and/or in the outer retina with disruption of the ellipsoid zone. During the inactive stage of the disease, the material disappeared or became hyperreflective and indistinguishable from the RPE. During the active stage of the disease, the area of hypoperfusion in the choriocapillaris significantly increased as visualized on both ICGA and SD-OCTA. CNV activity in 14 lesions was associated with subretinal material with a mixed reflectivity and hypotransmission of light to the choroid on SD-OCT and leakage on FA. SD-OCTA identified vascular structures in all active CNV lesions and in 24% of lesions without CNV activity (showing old, quiescent CNV membranes). CONCLUSION: Inflammatory activity in idiopathic MFC was associated with several MMI characteristics, including focally increased choroidal thickness. These characteristics can guide clinicians in the challenging process of the evaluation of disease activity in idiopathic MFC patients.

CORRELATION BETWEEN INFLAMMATORY FOCI REACTIVATION AND ATROPHY GROWTH IN EYES WITH IDIOPATHIC MULTIFOCAL CHOROIDITIS.

PURPOSE: To correlate the number of inflammatory reactivations in atrophic foci of multifocal choroiditis (MFC) with their growth rate over a 4-year span. METHODS: Comparative case series. Optical coherence tomography scans of patients affected by MFC were reviewed to identify reactivations within or at the margin of atrophic MFC foci. The area of selected lesions was semiautomatically delineated on fundus autofluorescence images and recorded at yearly intervals for a total follow-up of 4 years. The main outcome was the difference in annual square-root transformed area growth rate between lesions that reactivated and lesions that did not. RESULTS: Sixty-six foci of 30 eyes of 24 patients were included. All MFC foci enlarged over time, but the annual growth rate was more than double in lesions that reactivated compared with those that did not (mean [SD], 0.051 [0.035] vs. 0.021 [0.015] mm/year, P < 0.001), despite starting from comparable baseline areas. For each additional inflammatory reactivation, the annual growth rate increased by more than 20% (+0.009 mm/year, 95% CI [0.006, 0.012], P < 0.001). CONCLUSION: Increasing number of reactivations of atrophic foci led to proportional increments in their growth rate, highlighting the need for a tight control of inflammatory relapses in patients affected by MFC.

Multifocal Serpiginoid Choroiditis Due to Mycobacterium Mageritense following Laparoscopic Hysterectomy in an Immunocompetent Host.

PURPOSE: To report nontubercular choroiditis, caused by Mycobacterium mageritense isolated using MALDI-TOF MS, following laparoscopic hysterectomy in an immunocompetent patient. CASE REPORT: A 42-year-old female presented with gradual, painless diminution of vision in the right eye for six weeks. She had undergone laparoscopic hysterectomy two months back. BCVA was 2/60 OD. Clinical presentation and imaging all pointed to a diagnosis of serpiginous-like choroiditis. Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) had led to isolation of Mycobacterium mageritense. Patient was treated with systemic antibiotics. At 3 months follow up, BCVA improved to 6/60; fundus showed healed choroiditis and chorioretinal thinning. CONCLUSION: Atypical mycobacterial infections associated with laparoscopic surgeries can rarely lead to debilitating systemic bacteremia resulting in profound visual impairment. The importance of timely diagnosis using specific and sophisticated methods such as MALDI-TOF MS as well as maintaining aseptic precautions perioperatively during major surgeries cannot be overemphasized.

Multifocal choroiditis and choroidal tuberculoma: Signs of presumed ocular tuberculosis.

The diagnosis of OTB (Ocular tuberculosis) is usually difficult to make. Definitive diagnosis requires the identification of M. tuberculosis organisms in ocular tissues or fluids, but samples are often difficult to obtain, and biopsy may be hard to justify. We describe a 50-years-old Maghreb male, who presented a multifocal choroiditis associated with a choroidal tuberculoma on the left eye. Based on positive QuantiFERON-TB-Gold test and suggestive clinical and radiographic findings, a diagnosis of presumed ocular tuberculosis was made. Serial swept-source optical coherence tomography (SS-OCT) and widefield fundus retinographies during subsequent follow-up visits demonstrated the characterization of the atypical tuberculosis presentation and allowed the assessment of response to antitubercular therapy and oral steroids.

Comments on "Goyal M, Murthy SI and Annum S, Bilateral Multifocal Choroiditis following COVID-19 Vaccination".

The fundus photographs provided show deep yellowish lesions, multifocal exudative retinal detachments, and optic disc hyperemia in both eyes. Spectral domain optical coherence tomography scans shown demonstrate bilateral exudative retinal detachments involving the macula in the right eye. The exudative retinal detachment is characterized by the presence of subretinal fibrin and septa. The B-scan ultrasonography provided shows low- to medium-reflective choroidal thickening predominating around optic nerve head, in association with exudative retinal detachment in the right eye. All these findings are highly suggestive of acute Vogt-Koyanagi-Harada (VKH) disease rather than multifocal choroiditis.

COMPARISON OF PRIMARY AND SECONDARY FORMS OF MULTIPLE EVANESCENT WHITE DOT SYNDROME.

PURPOSE: The aim of this study was to compare primary versus secondary forms of multiple evanescent white dot syndrome (MEWDS) at T0 (baseline) and T1 (1-4 months after the onset of symptoms). METHODS: A total of 101 eyes in 100 patients were included in a multicentric retrospective study. RESULTS: Secondary MEWDS was defined as MEWDS associated with underlying chorioretinal inflammatory pathologies, mainly multifocal choroiditis and punctuate inner choroidopathy. Patients with secondary MEWDS were older (P = 0.011). The proportion of women (P = 0.8), spherical equivalent (P = 0.3), and best-corrected visual acuity at T0 (P = 0.2) were not significantly different between the two groups. The area of MEWDS lesions on late-phase indocyanine green angiography was significantly smaller in secondary MEWDS (P = 0.001) and less symmetrical with respect to both horizontal (P = 0.003) and vertical (P = 0.004) axis. At T0, neither the clinical (P = 0.5) nor the multimodal imaging (P = 0.2) inflammation scores were significantly different between the groups. At T1, the multimodal imaging inflammation score was higher in secondary MEWDS (P = 0.021). CONCLUSION: In secondary MEWDS, outer retinal lesions are less extensive and located close to preexisting chorioretinal lesions. Mild signs of intraocular inflammation on multimodal imaging are more frequent in secondary MEWDS during recovery. These findings suggest that chorioretinal inflammation may trigger secondary MEWDS.

MULTIMODAL IMAGING OF MULTIFOCAL CHOROIDITIS WITH ADAPTIVE OPTICS OPHTHALMOSCOPY.

PURPOSE: To describe longitudinal, anatomical, and functional alterations caused by inflammatory and neovascular lesions of idiopathic multifocal choroiditis/punctate inner choroidopathy using adaptive optics imaging and microperimetry. METHODS: Longitudinal case study using multiple imaging modalities, including spectral-domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, optical coherence tomography angiography, flood illumination adaptive optics, and microperimetry. RESULTS: A 21-year-old myopic Asian man presented with blurred vision in the right eye. Clinical examination was notable for an isolated hypopigmented, perifoveal lesion in each eye. Multimodal imaging showed inflammatory lesions in the outer retina, retina pigment epithelium, and inner choroid lesions of both eyes. The right eye additionally exhibited active Type-2 macular neovascularization with loss of cone mosaic regularity that was associated with reduced sensitivity on microperimetry. The clinical picture was consistent with multifocal choroiditis/punctate inner choroidopathy. The patient was treated with oral steroids and three injections of intravitreal bevacizumab in the right eye. After therapy, imaging showed reestablishment of the cone mosaic on flood illumination adaptive optics and improvement in sensitivity on microperimetry. CONCLUSION: Adaptive optics imaging and microperimetry may detect biomarkers that help to characterize the nature and activity of multifocal choroiditis lesions and to help monitor response to therapy. With timely intervention, structural abnormalities in the outer retina and choroid can be treated, and anatomical improvements precede improvements in visual function.

Bilateral multifocal choroiditis with disc edema in a 15-year-old girl following COVID-19 vaccination.

A few cases of posterior uveitis following COVID-19 vaccination have been reported but none in the pediatric age group. A 15-year-old girl presented with history of headache and bilateral blurred vision of five days duration. The symptoms developed five days after vaccination with the first dose of Covaxin (inactivated SARS-CoV-2 vaccine). Her anterior segment was normal in both eyes (BE), whereas the posterior segment showed mild vitritis with disc edema and multiple yellowish lesions at the level of choroid clustered at the macula and associated with multiple serous detachments. BE uveitis resolved, and the vision was completely recovered three weeks after treatment with steroids. Hence, ophthalmologists should be aware of uveitis following vaccination-a condition that is usually benign, transient, and results in excellent outcomes with timely diagnosis and early treatment with steroids.

Clinical case: Serpiginous-like choroiditis with macular involvement and good response after treatment with adalimumab.

Clinical case of a 42-year-old woman who consulted for decreased vision in the left eye over two months, associated with multifocal choroiditis. Different diagnostic tests were performed to rule out infectious pathologies, as well as a diagnostic vitrectomy test, which was negative. QuantiFERON® was found to be positive and a diagnosis of serpeginous-like choroiditis (SLC) was made. Anti-tuberculosis treatment was started with worsening of vision and multifocal choroiditis. Once conventional immunotherapy and biological treatment were added, the patient presented a significant improvement in vision. To conclude, in cases of CSL, it is not only necessary to treat the infection but also the inflammatory component either with steroids or conventional immunotherapy or immunosuppression with biologics, thus reducing the number of reactivations and improving the visual prognosis.

Idiopathic Multifocal Choroiditis and Punctate Inner Choroidopathy - Evaluation of Risk Factors for Increased Relapse Rate: A 2-Year Prospective Observational Cohort Study.

INTRODUCTION: The aim of this study was to describe the course of disease in patients with idiopathic multifocal choroiditis (MFC) and punctate inner choroidopathy (PIC) and to identify risk factors associated with an increased relapse rate of disease activity. METHODS: In this prospective observational cohort study, demographical and clinical data were collected concerning the relapses rate of disease activity, the conclusions of the multimodal imaging results, treatment, complications, and self-reported quality of life. Disease activity was defined as new inflammatory lesions or active inflammation in preexisting chorioretinal lesions either with or without active choroidal neovascularization (CNV). Linear regression analysis was performed to identify risk factors associated with an increased relapse rate. RESULTS: In total, 122 eyes of 82 patients (93% females) were included with a median age (IQR) of 45 (37-54) years. A history of secondary CNV was present in 66% of the eyes. During follow-up, the best-corrected visual acuity remained stable despite a median relapse rate (IQR) of 1.0 (0.25-3). Cycles of oral corticosteroids were given in 59% of the patients, 72% were treated at baseline or started treatment during follow-up with a disease-modifying antirheumatic drug (DMARD), and 35% with a biological agent in addition to the DMARD. Both a history of secondary CNV (B = 1.2, 95% CI: 0.7-1.7, p = 3.6 × 10-5) and high myopia (<-6 diopters) (B = 0.6, 95% CI: 0.1-1.1, p = 0.02) independently increased the relapse rate of disease activity. DISCUSSION/CONCLUSION: A history of secondary CNV and high myopia were associated with an increased relapse rate of disease activity. Moreover, the results of this study emphasize the challenging character of treating patients with MFC/PIC.

CLINICAL CHARACTERISTICS OF STREAKY MULTIFOCAL CHOROIDITIS: A Subtype of Multifocal Choroiditis.

PURPOSE: To describe and analyze clinical characteristics of multifocal choroiditis with linear streaks (LSs). METHODS: Eight cases of multifocal choroiditis with LSs were retrospectively studied. Multimodal imaging was performed. Demographic data and spherical equivalent were collected. Axial length was measured. RESULTS: All cases are young myopic women with a mean age of 17.13 ± 3.64 years (range, 13-23 years), presenting with vision loss and distortion. Nine eyes with LSs were high myopia of -8.97 ± 2.69 D (range, -6.00 to 12.5 D; growing by 1.88 ± 0.61 D annually since wearing glasses), with mean axial length of 26.36 ± 1.71 mm. Vitreous cells were noted in seven eyes. LSs were located in the equator (eight eyes), around the optic disk (three eyes), and at the edge of the posterior pole (one eye). Angio-optical coherence tomography showed choroidal neovascularization in eight eyes, especially 2 to 3 choroidal neovascularizations in three eyes. The location of choroidal neovascularization were in subfovea (three eyes), parafovea (six eyes), and perifovea (two eyes). Swept source optical coherence tomography showed punched-out disruption of retinal pigment epithelium‒Bruch's membrane‒choriocapillaris complex at the LSs' sites. LSs showed fluorescence staining on late FA but hypofluorescence throughout all phases on ICGA. CONCLUSION: Multifocal choroiditis with LSs mostly occurs in young women with high myopia, especially occurring in eyes with rapid progression of myopia. LSs are mainly located in the midperiphery near the equator, being prone to concur with choroidal neovascularization. Based on our findings, we propose a new term called "streaky multifocal choroiditis" as a subtype of multifocal choroiditis.