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.

Polypoidal choroidal vasculopathy 20 years after resolution of tubercular choroiditis.

We report the case of a 72-year-old white woman with blurring of vision in both eyes of 15 days' duration. She had a history of treatment for bilateral tuberculosis choroiditis 20 years before. She was diagnosed with polypoidal choroidal vasculopathy in the right eye and inflammatory choroidal neovascular membrane in the left eye, based on multimodal imaging, including optical coherence tomography, fundus fluorescein angiography, and indocyanine green angiography. The right eye received 3 intravitreal injections of aflibercept and showed complete resolution. The left eye was treated with a single intravitreal injection of aflibercept.

Punctate inner choroidopathy in common variable immunodeficiency associated with a pathogenic variant in the tumour necrosis factor receptor superfamily 13b (TNFRSF13B) gene - Case report and review of the literature.

BACKGROUND: Common variable immunodeficiency (CVID) has been recognised as the most common primary immunodeficiency in adulthood, and is characterised by increased susceptibility to infection, autoimmunity and increased risk of malignancies. Although ocular manifestations are not common in CVID, rare associated inflammatory eye conditions have been reported including submacular choroiditis. OBJECTIVE: To report a case of punctate inner choroidopathy in a patient with common variable immunodeficiency. CASE PRESENTATION: A 40-year-old lady with CVID and associated autoimmune thrombocytopenia, who was treated with immunoglobulin replacement and Eltrombopag, experienced gradually deteriorating right eye vision. Fundal examination and optical coherence tomography (OCT) revealed right multifocal retinal choroidal lesions consistent with a diagnosis of unilateral punctate inner choroidopathy (PIC) with secondary choroidal neovascularisation (CNV). Anti-VEGF injections led to stabilised fundal appearances. Genetic testing revealed a heterozygous sequence change c.260 T > Ap.(IIe87Asn), pathogenic variant in the Tumour Necrosis Factor Superfamily 13B (TNFRSF13B) gene, which is reported as being associated with ∼10% of CVID cases. CONCLUSION: Autoimmunity may be the dominant clinical presenting feature of CVID. Punctuate inner choroidopathy is an idiopathic inflammatory chorioretinopathy, and to the best of our knowledge, has not been previously reported in CVID. A better understanding of the molecular bases of autoimmune diseases in CVID may provide novel therapeutic targets for autoimmune diseases in this patient population.

Intraocular and neuro-cysticercosis with diffuse stromal choroiditis.

Intraocular cysticercosis with central nervous system involvement is not that rare. We report a male child with a right-sided painful blind eye who had intraocular cysticercosis and granuloma in the left frontal lobe of the brain. There was an incidental finding of chronic inflammation in the choroid of that eye supported by histopathology. Immunohistochemistry for T-cells marker and B-cells marker was variable. The patient was treated with antiparasitic, anti-epileptic medications, and oral steroids subsequently.

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.

Primary Sjögren's syndrome-related Choroiditis in a Newly Diagnosed Older Adult.

PURPOSE: To report a case of secondary bilateral choroiditis in a patient with primary Sjögren's syndrome(pSS). STUDY DESIGN: Case report. RESULTS: A 69-year-old woman visited our hospital for consultation due to decreased visual acuity in both eyes for 1 month. At the first visit, best corrected visual acuity (BCVA) was 0.2 and 0.3 in her right and left eyes, respectively. Intraocular pressure values were 15 mmHg and 16 mmHg in her right and left eyes, respectively. Examination revealed edema of the eyelids and conjunctiva,and corneal fluorescence staining was positive. No inflammation in the anterior chamber or vitreous opacities were observed. Bilateral multiple retinal detachments were observed on the posterior fundus, and optical coherence tomography revealed bilateral multiple areas of retinal neuroepithelial detachment, choroidal thickening, and choroidal folds. No abnormal fluorescence leakage was observed on fundus fluorescein angiography or indocyanine green angiography. In addition, systematic manifestations included recurrent bilateral parotid gland enlargement. Labial gland biopsy revealed dilated glandular ducts, scattered interstitial glands, and lymphocytic foci. Salivary gland scintigraphy revealed severe impairment of glandular excretory function. Moreover, blood tests for anti-Ro/SSA and anti-La/SSBantibodies were positive. The patient was diagnosed with primary Sjögren's syndrome. After 2 months treatment with oral prednisolone acetate combined with hydroxychloroquine, her BCVAimproved to 0.8 and 1.0 in the right and left eyes, respectively. The fundus also recovered to normal, and no recurrence was observed during the 1-year follow-up period. CONCLUSIONS: The current case highlights that pSS, which usually manifests with dry eye and keratoconjunctivitis, may manifest with chronic choroiditis in both eyes as well. Based on our experience with this case, patients with clinically suspected bilateral choroiditis should be evaluated for pSS.

Outcomes of adalimumab therapy in refractory punctate inner choroidopathy and multifocal choroiditis.

PURPOSE: This study aims to evaluate the outcomes of adalimumab (ADA) therapy in patients with refractory punctate inner choroidopathy (PIC) and multifocal choroiditis (MFC). METHODS: Demographic and clinical data, including LogMAR best-corrected visual acuity (BCVA), were retrospectively collected. Doses of prednisone, immunomodulatory therapies (IMT), and anti-vascular endothelial growth factor (VEGF) injections before and after baseline (ADA initiation) were recorded, as well as the time to clinical remission, time to first flare, and drug-associated adverse events. RESULTS: Seven patients (4 females, ten eyes) were included. The mean follow-up after baseline was 17.8 ± 11.1 months (range 6-33). The mean LogMAR BCVA was 0.35 ± 0.77 at 6 months before baseline and remained stable throughout 12 months after baseline (0.31 ± 0.46 at 12 months; p = 0.47). The mean dose of prednisone decreased from 17.3 ± 19.6 mg/day 6 months before baseline (range 0-60) to 2.6 ± 2.4 mg/day at the last follow-up (range 0-6, p = 0.03). The mean number of flares decreased significantly from 1.43 ± 0.79 over a 6-month period before baseline to 0.2 ± 0.45 (p = 0.02) at 6-12 months after baseline. The mean number of anti-VEGF injections was 4.17 ± 3.92 over the 12-month period before baseline, and it was 2.17 ± 3.06 (p = 0.31) during the first 12 months after baseline. No adalimumab-related adverse events were noted. CONCLUSION: Adalimumab therapy for refractory PIC/MFC enabled a significant steroid-sparing effect, decreased disease flares, and preserved vision over a mean follow-up of 17.8 months.

Idiopathic multifocal choroiditis and punctate inner choroidopathy: an evaluation in pregnancy.

PURPOSE: To evaluate the clinical course of idiopathic multifocal choroiditis (MFC) and punctate inner choroidopathy (PIC) and the efficacy and safety of treatment options during pregnancy. METHODS: Patients with MFC or PIC and a pregnancy in 2011-2019 from two academic centres were enrolled. For the most recent pregnancy, data on best-corrected visual acuity (BCVA) before and after pregnancy, relapse rate in pregnancy and postpartum period and obstetric, maternal and neonatal outcomes were collected. Treatment regimens consisted of a wait-and-see regime and an immunosuppressive treatment regime with systemic corticosteroids and/or azathioprine, both combined with intravitreal antivascular endothelial growth factor injections when indicated. RESULTS: Sixteen women (26 affected eyes) were included. Median Snellen BCVA was 20/19 before pregnancy and 20/18 after delivery. In seven pregnancies a wait-and-see regime and in nine pregnancies an immunosuppressive treatment regime was carried out. Fourteen intravitreal anti-VEGF injections were given in six pregnancies. The relapse rate during pregnancy was 44% and in the postpartum period 31%. Maternal/obstetrical and fetal complications occurred in 31% and 13% of the pregnancies, respectively. Fifteen healthy children were born and one pregnancy ended in a stillbirth in a patient with a complicated obstetrical history. One patient treated with azathioprine developed intrahepatic cholestasis of pregnancy (ICP). CONCLUSIONS: Among women with MFC and PIC BCVA remained stable during pregnancy despite a relapse rate of 44% in pregnancy. No major maternal, obstetric and fetal complications occurred in pregnant patients treated with systemic corticosteroids, azathioprine or intravitreal anti-VEGF injections, though one patient developed ICP while treated with azathioprine.

Distinct recurrence pattern in a case of bilateral tubercular posterior uveitis: reporting a unique clinical morphology and management challenge.

Intraocular tuberculosis has protean clinical manifestations and remains an important etiological differential for uveitis in an endemic region. A 27-year-old male presented with visual acuity of counting fingers close to face in right (OD) and 20/25 in left eye (OS). Examination revealed a choroidal granuloma in OS and healed serpiginous-like choroiditis in OD. Antitubercular therapy was started with systemic corticosteroids. Granuloma resolved completely; however, the patient presented with neuroretinitis and posterior scleritis, as first and second recurrence, respectively, within a oneyear period. These were managed with systemic corticosteroids and immunosuppressive therapy was added, after second recurrence. The patient responded well and maintains remission. This case presented a clinical challenge with distinct recurrence patterns of tubercular posterior uveitis in the same eye, which has not been reported before. Successful management entailed use of antitubercular therapy, corticosteroids, and immunosuppressive therapy in a step-ladder approach, resulting in preservation of vision and achieving long-term remission.

The Use of Optical Coherence Tomography Angiography in the Diagnosis of Inflammatory Type 1 Choroidal Neovascularization Secondary to Tuberculosis: A Case Report.

Purpose: To report a case of choroidal neovascularization (CNV), which was not obvious with dye angiography but was detected with optical coherence tomography angiography (OCTA).Methods: A 50-year-old female presented with decreased vision in her right eye. Funduscopic examination revealed a swollen hyperemic disc, peripapillary exudation, and choroidal infiltration.Results: Optical coherence tomography revealed intraretinal cysts, subretinal fluid in the macular region, and subretinal hyperreflective material in the papillomacular area. Fluorescein angiography revealed early hypofluorescence in the areas of choroidal infiltrations, and indocyanine green angiography (ICGA) also showed hypocyanescence corresponding to these infiltrations and revealed a faint hypocyanescence in the papillomacular region, further corresponding to the subretinal hyperreflective material on OCT scan. Two weeks after the initiation of systemic therapy with the diagnosis of tuberculosis, OCTA scans detected Type 1 CNV in the peripapillary area.Conclusion: OCTA may be superior to ICGA in the detection of CNV secondary to inflammatory situations.

Inflammatory choroiditis and papillitis from Crohn's disease in a child.

A 5-year-old boy had subacute painless visual loss in his left eye with disk edema, macular edema, and choroidal thickening. He was subsequently diagnosed with inflammatory papillitis and choroiditis from Crohn's disease. The disk and macular edema responded minimally to antivascular endothelial growth factor injections but significantly to intravitreal corticosteroids.

Systemic Immunosuppression Is Highly Effective in the Long-term Control of Inflammatory non-infectious Uveitic Choroidal Neovascularization: A Comparative Study.

Purpose: To compare immediate versus delayed introduction of immunosuppressives for naive noninfectious inflammatory choroidal neovascularization (iCNV).Methods: a retrospective, consecutive, comparative, interventional case series of patients with a diagnosis of inflammatory CNV and a minimum follow of 36 months. Patients were divided into two groups: Group A received Immunosuppressives if needed, while Group B since baseline. Both groups received systemic steroids and intravitreal ranibizumab since baseline. Primary end point was to compare the BCVA outcome till 36-month follow-up.Results: Twenty-nine eyes with iCNV were enrolled. In the long term, best-corrected visual acuity (BCVA) was significantly better in group B. At 3-month follow-up, Group B reduced steroids <10 mg/day significantly (p = .0001, Fisher's Exact Test). At 36 months of follow up, injections given were 2.9 (0.9 SD) in group A and 1.25 (0.4 SD) in group B.Conclusion: early immunosuppressive therapy exerts a positive action on the long-term control of uveitic CNV.

Fursultiamine Alleviates Choroidal Neovascularization by Suppressing Inflammation and Metabolic Reprogramming.

Purpose: To assess the therapeutic effects of fursultiamine on choroidal neovascularization (CNV) through its modulation of inflammation and metabolic reprogramming in the retinal pigment epithelium (RPE). Methods: The anti-angiogenic effects of fursultiamine were assessed by measuring vascular leakage and CNV lesion size in the laser-induced CNV mouse model. Inflammatory responses were evaluated by quantitative polymerase chain reaction, western blot, and ELISA in both CNV eye tissues and in vitro cell cultures using ARPE-19 cells or primary human RPE (hRPE) cells under lipopolysaccharide (LPS) treatment or hypoxia. Mitochondrial respiration was assessed by measuring oxygen consumption in ARPE-19 cells treated with LPS with or without fursultiamine, and lactate production was measured in ARPE-19 cells subjected to hypoxia with or without fursultiamine. Results: In laser-induced CNV, fursultiamine significantly decreased vascular leakage and lesion size, as well as the numbers of both choroidal and retinal inflammatory cytokines, including IL-1ß, IL-6, IL-8, and TNF-α. In LPS-treated ARPE-19 cells, fursultiamine decreased proinflammatory cytokine secretion and nuclear factor kappa B phosphorylation. Furthermore, fursultiamine suppressed LPS-induced upregulation of IL-6, IL-8, and monocyte chemoattractant protein-1 in a dose-dependent and time-dependent manner in primary hRPE cells. Interestingly, fursultiamine significantly enhanced mitochondrial respiration in the LPS-treated ARPE-19 cells. Additionally, fursultiamine attenuated hypoxia-induced aberrations, including lactate production and inhibitory phosphorylation of pyruvate dehydrogenase. Furthermore, fursultiamine attenuated hypoxia-induced VEGF secretion and mitochondrial fission in primary hRPE cells that were replicated in ARPE-19 cells. Conclusions: Our findings show that fursultiamine is a viable putative therapeutic for neovascular age-related macular degeneration by modulating the inflammatory response and metabolic reprogramming by enhancing mitochondrial respiration in the RPE.

Unilateral multifocal choroiditis following EBV-positive mononucleosis responsive to immunosuppression: a case report.

BACKGROUND: Multifocal choroiditis (MFC) is a relatively uncommon bilateral inflammatory chorioretinopathy affecting Caucasian young women with myopia. We present images from a case of completely unilateral multifocal choroiditis following EBV-positive mononucleosis that demonstrated a dramatic clinical response to immunosuppression. CASE PRESENTATION: A 20-year-old woman with bilateral high myopia (-6D) and a documented normal prior retinal examination presented with visual loss in the right eye 2 months following confirmed Epstein-Barr virus (EBV) positive mononucleosis. Ophthalmoscopic examination showed completely unilateral placoid lesions of variable age. The left eye was unaffected. Fluorescein angiography revealed active leakage, especially in the parafovea. Spectral domain optical coherence tomography (SD-OCT) demonstrated sub-retinal pigment epithelial nodular deposits, some of which were confluent with overlying intra-retinal fluid and indistinct margins. Upon treatment with the immunosuppressant azathioprine there was significant resolution of the lesions in her right eye along with improvement in vision. CONCLUSION: This is a rare case of completely unilateral MFC following an episode of EBV positive mononucleosis that showed a dramatic response to immunosuppression.

Persistent Placoid Maculopathy: Prognosis Factors and Functional Outcomes.

Purpose: To identify prognosis factors and functional outcomes of persistent placoid maculopathy (PPM). Methods: We collected personal PPM cases and combined them with the data from the literature. Results: 68 eyes of 37 patients with PPM were analyzed, including six new cases. Twenty-six patients were men (70%) with a mean age of 51.8 years old. The mean initial visual acuity (VA) was 0.52 LogMar ± 0.55 for a mean final VA of 0.49 LogMar ± 0.51. Risk factors for poor VA included: initial VA less than 0.2 LogMar (p < .0001), cardiovascular risk factor (p = .008), autoimmune-related and/or systemic pro-inflammatory conditions (p = .003), choroidal neovascularization (p = .001), macular atrophy (p = .03) and absence of systemic corticosteroid treatment (p = .03). Conclusion: PPM is a choroidal inflammation. Identifying prognosis factors may help to guide treatment and follow-up. We showed that anti-inflammatory drugs, and anti-VEGF injections in cases of choroidal neovascularization, may lead to better outcomes.

Longitudinal analysis of serum cytokine profile among patients with tubercular multifocal serpiginoid choroiditis: a pilot study.

PURPOSE: To analyze the serum cytokines profile in patients with tubercular multifocal serpiginoid choroiditis (TB MSC) receiving anti-tubercular therapy (ATT) and oral corticosteroids. METHODS: In this prospective longitudinal study, patients with active TB MSC were included. Serum levels of interferon (IFN)-γ, interleukin (IL)-10, and tumor necrosis factor (TNF)-α were analyzed using bead-based immunoassay. The levels of transforming growth factor (TGF)-ß were measured using cytokine bead array. Serial measurement was performed at baseline, 1, 3, and 6 weeks after initiation of therapy. Patients developing paradoxical worsening (PW) of TB MSC were identified and their serum levels of cytokines were compared with those patients who showed healing of lesions. Comparison of cytokine levels with baseline values was also performed. RESULTS: Twelve patients (three females) were included in the study. Four patients showed paradoxical worsening of TB MSC at 3.2 ± 1 weeks after initiation of therapy. Compared to patients who showed healing of lesions, patients with PW showed higher baseline IL-10 (not significant; p = 0.28). Among patients developing PW, levels of IFN-γ peaked at 1 week ((p = 0.01) and levels of TNF-α peaked at 3 weeks (p = 0.02) (coinciding with PW) compared to patients who showed healing. There was no significant difference in TGF-ß levels at any time point in either group (p > 0.47). CONCLUSIONS: Baseline and serial levels of inflammatory serum cytokines may help in predicting the response to ATT and corticosteroids in TB MSC. Patients with paradoxical worsening may show rise in pro-inflammatory cytokines after initiation of ATT indicating higher bacillary load.

Case of cryptococcal choroiditis in adult with T-cell leukemia/lymphoma.

A rare case of 70-year-old woman with adult T-cell leukemia/lymphoma who developed multifocal choroiditis from a dissemination of Cryptococcus neoformans is reported. Ophthalmologic examination revealed multiple yellowish choroidal lesions in the posterior pole of both eyes. Sequential optical coherence tomographic images disclosed the involvement of the choroid and the consecutive changes in its architecture during the course of treatment. The recognition of these ocular manifestations may be important for the rapid diagnosis of C. nerformans-disseminated diseases. Rapid diagnosis and prompt therapy with intravitreal injection as well as systemic fosfluconazole and liposomal amphotericin B led to clinical improvement of intraocular cryptococcosis.

Intravitreal anti-VEGF treatment for choroidal neovascularization secondary to punctate inner choroidopathy.

PURPOSE: To assess the outcome of patients with choroidal neovascularization (CNV) secondary to punctate inner choroidopathy (PIC) receiving intravitreal anti-VEGF (vascular endothelial growth factor) injections. METHODS: Sixteen eyes of 16 patients diagnosed with CNV secondary to PIC were retrospectively assessed. RESULTS: Eleven women and five men with a mean age of 35 years (SD 11, range 16-56 years) received intravitreal anti-VEGF for PIC-related CNV. On average, 3.5 injections (SD 2.7, range 1-9) were given per eye. Thirteen eyes were treated with bevacizumab, two eyes with ranibizumab and one eye received both substances. The mean follow-up was 15 months (SD 11, range 6-40 months). BCVA improved in eight eyes (mean Δ +2.8 lines), remained stable in four eyes and decreased in four eyes (mean Δ -4.3 lines). CONCLUSIONS: CNV development is a frequent complication of PIC. Intravitreal anti-VEGF therapy seems to be safe and effective for PIC-related CNV.