Diagnostic Challenges in Inflammatory Choroidal Neovascularization.

Inflammation plays a key role in the induction of choroidal neovascularization (CNV). Inflammatory choroidal neovascularization (iCNV) is a severe but uncommon complication of both infectious and non-infectious uveitides. It is hypothesized that its pathogenesis is similar to that of wet age-related macular degeneration (AMD), and involves hypoxia as well as the release of vascular endothelial growth factor, stromal cell-derived factor 1-alpha, and other mediators. Inflammatory CNV develops when inflammation or infection directly involves the retinal pigment epithelium (RPE)-Bruch's membrane complex. Inflammation itself can compromise perfusion, generating a gradient of retinal-choroidal hypoxia that additionally promotes the formation of choroidal neovascularization in the course of uveitis. The development of choroidal neovascularization may be a complication, especially in conditions such as punctate inner choroidopathy, multifocal choroiditis, serpiginous choroiditis, and presumed ocular histoplasmosis syndrome. Although the majority of iCNV cases are well defined and appear as the "classic" type (type 2 lesion) on fluorescein angiography, the diagnosis of iCNV is challenging due to difficulties in differentiating between inflammatory choroiditis lesions and choroidal neovascularization. Modern multimodal imaging, particularly the recently introduced technology of optical coherence tomography (OCT) and OCT angiography (noninvasive and rapid imaging modalities), can reveal additional features that aid the diagnosis of iCNV. However, more studies are needed to establish their role in the diagnosis and evaluation of iCNV activity.

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.

A case of tubulointerstitial nephritis and uveitis syndrome accompanied by subclinical choroiditis.

BACKGROUND: Tubulointerstitial nephritis and uveitis (TINU) syndrome is an uveits characterized by complications of idiopathic acute tubulointerstitial nephritis, and most cases present only anterior uveitis. We report a case of TINU syndrome in which the presence of choroiditis was revealed by multimodal imaging. CASE PRESENTATION: A 12-year-old male visited our hospital with a 6-day history of ocular pain and hyperemia. Conjunctival and ciliary injections, 1 + flare and 3 + cells of anterior chamber inflammation with mutton fat keratic precipitates were observed in both eyes (OU), together with redness and swelling of the optic disc OU. Laboratory tests showed slightly high levels of soluble IL-2R and serum ß2 microglobulin and markedly high levels of urinary ß2 microglobulin. The diagnosis of probable TINU syndrome was established on the basis of bilateral uveitis and urinalysis results in accordance with a clinical criteria of tubulointerstitial nephritis. With treatment with oral prednisolone (PSL) at 20 mg/day, ocular findings improved, and the dose of PSL was gradually reduced and withdrawn 6 months later. However, 1 month later from the withdrawal, ocular inflammation recurred with the presence of retinal exudates and snowball vitreous opacities in the peripheral retina OU. Fluorescein angiography showed leakages from peripheral retinal vessels and staining corresponding to retinal exudates. Indocyanine green angiography showed hypofluorescent dots scattered over the ocular fundus. Optical coherence tomography revealed the presence of choroidal thickening. Laser speckle flowgraphy color map showed a relatively cooler color. Findings from these multimodal images indicated the presence of subclinical choroiditis; therefore, oral PSL was administered again, and ocular inflammatory findings were improved. CONCLUSIONS: TINU syndrome can exhibit subclinical choroiditis detected with multimodal imaging. Further studies are necessary to determine the frequency of subclinical choroiditis in TINU syndrome.

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.

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.

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.

OCULAR BARTONELLOSIS PRESENTING WITH FOCAL CHOROIDITIS, FOCAL RETINITIS, BRANCH RETINAL ARTERY OCCLUSION, AND PARACENTRAL ACUTE MIDDLE MACULOPATHY: LONGITUDINAL MULTIMODAL IMAGING ANALYSIS.

BACKGROUND/PURPOSE: To report an atypical case of ocular bartonellosis evaluated longitudinally with multimodal imaging and review the literature on the less common posterior segment manifestations of bartonella infection. METHODS: Case report and review of the literature. RESULTS: A 26-year-old man presented with focal choroiditis in the right eye and focal retinitis, a branch retinal artery occlusion, and paracentral acute middle maculopathy in the left eye after a systemic prodrome including headache and lymphadenopathy. Serologic testing revealed positive bartonella immunoglobulin G with a titer of 1:512. The patient was diagnosed with ocular bartonellosis infection and started on systemic doxycycline. The posterior segment findings resolved over the follow-up period, and their resolution was documented with optical coherence tomography. CONCLUSION: Neuroretinitis is the classic ocular finding in cat scratch disease, but less common presenting findings may include focal choroiditis, retinitis, and branch retinal artery occlusion. To the best of our knowledge, this is the first report of paracentral acute middle maculopathy secondary to a retinitis-associated branch retinal artery occlusion as a presenting sign in ocular bartonellosis.

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.

Chorioretinal Atrophy in Punctate Inner Choroidopathy/multifocal Choroiditis: A Five-year Follow-up Study.

PURPOSE: To report the 5-year results of chorioretinal atrophy (CRA) progression in patients with punctate inner choroidopathy (PIC) or multifocal choroiditis (MFC). METHODS: A retrospective study included PIC/MFC patients with secondary CRA formation. The area of CRA was measured and the progression rate was calculated. Multiple regression analysis was performed to investigate risk factors associated with CRA progression. RESULTS: Forty-five eyes of 36 patients were included. The mean CRA size significantly increased after an average of 4.83 years of follow-up with progression rate of 0.69 mm2/year. Moreover, we had identified the axial length and initial PIC lesion number as significant risk factors for CRA progression. CONCLUSION: Significant CRA enlargement is noted in PIC/MFC patients after 5 years of follow-up. The progression rate is associated with axial length and initial PIC numbers. Aggressive treatment is suggested for eyes with more initial lesion numbers and longer axial length to control the faster CRA progression.

Rapid progression of chorioretinal atrophy in punctate inner choroiditis: a case report.

BACKGROUND: The chorioretinal inflammatory lesions occurring in punctate inner choroiditis evolve into punched-out atrophic scars. Typically, the progression is gradual. We report a case of highly myopic punctate inner choroiditis with rapid progression of chorioretinal atrophy. CASE PRESENTATION: A 48-year-old Japanese woman with high myopia presented with decreased visual acuity. Best-corrected visual acuity was 20/28 in the right eye and 20/16 in the left eye; axial length was 29.0 mm and 28.7 mm, respectively. Fundoscopy revealed an epiretinal membrane in the left eye. Three years later, the best-corrected visual acuity in the left eye had decreased to 20/33; at this time, the patient underwent vitrectomy with epiretinal membrane and internal limiting membrane peeling in this eye. Six months later, the best-corrected visual acuity in the left eye decreased suddenly to 20/100. Optical coherence tomography showed a nodule-like lesion in the outer retina with disruption of the retinal pigment epithelium and a focally thickened choroid, compatible with PIC. One month later, the choroidal thickness had decreased. The central chorioretinal atrophy expanded rapidly at a rate of 0.45 mm2/year over the next 3 years, and new areas of patchy focal chorioretinal atrophy developed in the perifovea. CONCLUSIONS: Rapid progression of chorioretinal atrophy was observed in a patient with punctate inner choroiditis. Because punctate inner choroiditis is often associated with degenerative myopia, the retina is fragile and may be susceptible to mechanical damage. This case report alerts clinicians to the need for careful management of patients with punctate inner choroiditis, especially after vitrectomy.

Serpiginous Choroiditis Complicated with Choroidal Neovascular Membrane Detected using Optical Coherence Tomography Angiography: A Case Series and Literature Review

Serpiginous choroiditis (SC) is a rare, chronic, recurrent, progressive disease of unknown origin. The inflammatory process of SC can disrupt Bruch's membrane, allowing occasional choroidal vascular growth, leading to significant visual loss even in the healed stages of the disease. Optical coherence tomography angiography (OCTA) can help in the detection of choroidal neovascular membrane (CNV), leading to a definitive diagnosis and thereby guide the initiation of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment. We report herein two cases of SC complicated with a CNV detected with OCTA and treated with a series of anti-VEGF injections.

TUBERCULOUS CHOROIDITIS IN PATIENT WITH VOGT-KOYANAGI-HARADA DISEASE.

PURPOSE: To describe a novel case of intraocular tuberculosis (TB) arising in a patient undergoing treatment for Vogt-Koyanagi-Harada disease, and to highlight the use of spectral domain optical coherence tomography for helping confirm the diagnosis and monitor treatment response. METHODS: Case report of a patient with Vogt-Koyanagi-Harada disease on prednisone, with acute clinical changes suspicious for bilateral tuberculous choroiditis. Spectral optical coherence tomography, fundus photography, and B-scan ultrasonography were all used to capture the acute lesions, and to monitor their responses after initiation of anti-TB therapy. RESULTS: New subretinal lesions arose bilaterally, as characterized by spectral domain optical coherence tomography, and appeared to regress after a first round of anti-TB therapy, thereby helping confirm the presumed diagnosis of intraocular TB. A new peripheral choroidal lesion arose shortly after temporary cessation of antimicrobial treatment, and again regressed once four-drug therapy was instituted, with no recurrent lesions thereafter. CONCLUSION: The use of multimodal imaging was instrumental in the management of a rare case of intraocular TB arising in the setting of underlying Vogt-Koyanagi-Harada disease.

Manejo da coroidite interna punctata complicada por membrana neovascular sub-retiniana / Management of punctate inner choroidopathy complicated by subretinal neovascular membrane

RESUMO Este trabalho visou evidenciar a importância da detecção precoce da coroidite interna punctata e destacar sua fisiopatologia inflamatória e possíveis diagnósticos diferenciais dentro das white dot syndromes. O destaque foi dado principalmente à coroidite multifocal e à panuveíte, ao se demonstrar sua epidemiologia peculiar em mulheres jovens, caracterizar sua apresentação clínica típica na fundoscopia e explorar as vantagens e as desvantagens de realizar os exames complementares que fazem parte da análise multimodal útil para o diagnóstico (especialmente a angiografia fluoresceínica, a tomografia de coerência óptica e a indocianina verde). Descreve-se o caso de uma mulher de 28 anos diagnosticada com coroidite interna punctata com membrana neovascular coroidal em olho direito. O tratamento foi realizado com injeção intravítrea de aflibercepte e corticoterapia sistêmica 1mg/kg ao dia. Este relato é importante por permitir debater o manejo da coroidite interna punctata durante a gestação e a decisão de realizar o tratamento mediante uma diversidade de opções terapêuticas.

ABSTRACT This work aimed to demonstrate the importance of early detection of punctate inner choroidopathy, highlighting the pathophysiology of inflammation and the differential diagnoses among white dot syndromes. Special attention was given to multifocal choroiditis and panuveitis, by demonstrating the peculiar epidemiology in young women, characterizing the typical clinical presentation in ophthalmoscopy, and exploring the advantages and disadvantages of performing the complementary examinations, which are part of the multimodal analysis useful for diagnosis (particularly fluorescein angiography, optical coherence tomography, and indocyanine green). We report the case of a 28-year-old female, diagnosed as punctate inner choroidopathy with choroidal [N.T. no título aparece subretinal = subrretiniana] neovascular membrane in the right eye. She was treated with intravitreal injection of aflibercept and systemic corticosteroid 1 mg/kg/day. This case report is important for addressing the management of punctate inner choroidopathy during pregnancy, and the decision to carry out treatment considering diverse therapeutic options.

Optic Disc Neovascularization in Tubercular Serpiginous-Like Choroiditis.

Optic disc neovascularization in uveitis is uncommon, and has been associated with chronic inflammations like Behcet's disease, Vogt-Koyanagi-Harada disease, sarcoidosis, etc. To our knowledge, optic disc neovascularization has not been reported in tubercular serpiginous-like choroiditis. We report three such cases.

Bilateral diffuse retinal pigment epithelium proliferation induced by choroidal inflammation: A case report.

RATIONALE: Proliferation of retinal pigment epithelium (RPE) is typically observed in limited ocular disorders, in connection with the local mechanism of RPE proliferation-mediated wound repair. Bilateral and diffuse type RPE proliferation is considered to be associated with paraneoplastic syndromes, such as a bilateral diffuse uveal melanocytic proliferation. However, other reported diseases that induce bilateral diffuse RPE proliferation are quite rare, especially for patients who are considered to have a non-malignant status. PATIENT CONCERNS: The bilateral eyes of a 47-year-old woman with bilateral ocular inflammation, presented united multiple small to medium white retinal lesions during the disease progress. DIAGNOSES: Optical coherence tomography showed scattered serous retinal detachments, choroidal folds, choroidal thickening and diffuse RPE proliferation. As autofluorescence and angiography showed a "giraffe pattern", bilateral diffuse uveal melanocytic proliferation was suspected. However, systemic investigations identified no malignancy. In consideration of the above findings, choroidal inflammation was thought to be the major cause of this condition. INTERVENTIONS: The patient was administered intensive systemic steroids. Over the next 2 months, the amount of steroid was tapered off. OUTCOMES: After administration, the bilateral diffuse RPE proliferation settled down. During the 2-year follow-up, there was no recurrence of ocular inflammation and diffuse RPE proliferation, or any other malignancy found. LESSONS: This finding demonstrates that bilateral diffuse RPE proliferation can be generated as a secondary phenomenon of choroidal inflammation in patients with a non-malignant status.