Bilateral Granulomatous Uveitis Research Articles

Correlation of Mantoux Test and Serum Angiotensin-Converting Enzyme (ACE) Levels with Clinically and Radiologically Diagnosed Ocular Tuberculosis and Ocular Sarcoidosis

Abstract Aim: To evaluate the role of combined Mantoux test and serum angiotensin-converting enzyme (ACE) levels in the diagnosis of ocular tuberculosis (TB) and ocular sarcoidosis. Materials and Methods: A prospective and observational study including patients with bilateral granulomatous uveitis diagnosed both radiologically and clinically as ocular TB or ocular sarcoidosis within a six-month period. CT Thorax/CT abdomen was done, and findings were noted. Mantoux test and serum ACE levels were recorded, and findings were correlated. Results: The study included a total of 60 patients: 32 patients with ocular TB and 28 patients with ocular sarcoidosis. Using Mantoux test, 84.4% in the TB group tested positive and were correctly identified (sensitivity), and 96.4% in the sarcoid group tested negative and were correctly identified as sarcoidosis. Hence, the association between Mantoux test and diagnoses was statistically significant (P < 0.001). In the TB group, 25 subjects had normal and seven had elevated serum ACE levels. In the sarcoidosis group, 22 subjects had elevated and six had normal serum ACE levels. Hence, 78.1% were correctly identified with normal serum ACE levels (sensitivity) in the TB group and 78.6% were identified with elevated serum ACE levels in the sarcoidosis group, and the proportion difference was statistically significant (P < 0.001). Conclusion: Mantoux test and serum ACE levels are cost-effective investigations and can be used for the diagnosis of ocular TB and sarcoidosis when combined with clinical and radiological evidence. The combined use of serum ACE and Mantoux test is useful in differentiating between sarcoidosis and TB.

Sarcoidosis‐related uveitis: A case series study

Purpose: The aim of this study was to characterize the epidemiological and clinical characteristics of ocular involvement in patients with systemic sarcoidosis.Methods: Retrospective case series study carried out at the Ophthalmology department of Habib Thameur University Hospital of Tunis between the 1st January 2022 and the 1st January 2023. Fifteen patients (30 eyes) were included. Based on the International Workshop on Ocular Sarcoidosis criteria, three patients had biopsy‐proven sarcoidosis; eight had presumed sarcoidosis and four had probable sarcoidosis. All patients had a complete ocular examination and systemic work‐up.Results: The median age at presentation was 45 years (range: 29–66). The sex ratio was 1:13. Ocular involvement was the presenting symptom in 11 patients. Bilateral granulomatous uveitis was the presenting form in all patients. Panuveitis was the most common anatomic pattern (9), followed by anterior (3), anterior and intermediate (2) and intermediate (1) uveitis. Posterior segment involvement included multifocal choroiditis (3) retinal vasculitis (5) macular oedema (4) and optic nerve head granuloma (1). Systemic manifestations included bilateral hilar lymphadenopathy (8) eyelid granuloma (2) neurosarcoidosis (3) Peripheral facial nerve palsy (2).Conclusions: Uveitis was the initial presentation of sarcoidosis in the majority of our subjects. Panuveitis was the most commonly encountered anatomic form. Our findings support the prominent role of the ocular examination in the early detection of sarcoidosis.

Post-COVID-19 vaccine uveitis: A case series

With the recent emergence and worldwide distribution of COVID-19 vaccines, many side effects may be underreported and possibly unknown. Cases of vaccine-associated uveitis have been linked to almost all vaccines administered in the past; however, there is scarcity of literature providing insight into post-COVID-19 vaccine-associated uveitis. This case series documents patients presenting with uveitis after administration of the Pfizer and Moderna mRNA vaccines, in hope of advancing our current understanding of potential ocular complications of COVID-19 vaccines. Patients with ocular symptoms consistent with uveitis within 14 days after administration of the Pfizer or Moderna COVID-19 vaccines were included in this case series. Eight patients with a mean age of 44.4 years (range, 19-83) were included. Six patients received a Pfizer, and 2 received a Moderna vaccine. Four patients presented after their first dose, 3 after their second dose, and 1 after both doses. The mean onset of ocular symptoms after the vaccine was 5.19 days (range, 1-14), and the mean BCVA was 0.678. Patients were diagnosed with bilateral anterior granulomatous uveitis (case 1), unilateral non-granulomatous anterior uveitis (case 2, 5-8), and bilateral non-granulomatous anterior uveitis (case 3-4). The pathogenesis of vaccine-induced uveitis is not properly understood; however, the outcomes of this case series will aid in establishing a temporal association between the Pfizer and Moderna COVID-19 vaccines and the onset of uveitis. As the rate of COVID-19 vaccinations increases globally, it is imperative for physicians to be aware of the possible association and presentation of these ocular findings and diagnoses in order to treat patients effectively.

Chinese expert consensus on the clinical diagnosis and treatment of Vogt-Koyanagi-Harada syndrome (2023)

Vogt-Koyanagi-Harada (VKH) syndrome is an autoimmune disorder characterized by bilateral granulomatous uveitis, and it is one of the common uveitis entities causing blindness in China. The clinical manifestations of VKH disease vary significantly at different stages. Most patients can achieve a complete control of the uveitis and good visual prognosis if appropriate treatment is initiated. Therefore, an extensive investigation and literature review on this disease have been performed by the experts in the Uveitis and Ocular Immunology Group of Chinese Ophthalmologist Association and the Ocular Immunology Group of Ophthalmology Society of Chinese Medical Association. Consensus opinions on VKH syndrome have been developed in an attempt to provide general guidance and reference in the diagnosis and treatment of this disease.

An atypical presentation of sympathetic ophthalmia following chemical ocular burns

BackgroundSympathetic ophthalmia is a rare disease that can present as bilateral granulomatous uveitis after a penetrating trauma or surgery in one eye.FindingsWe report a case of a 47-year-old male with history of decreased vision in the right eye, six months after sustaining severe chemical injury in the left eye. He was diagnosed with sympathetic ophthalmia and was treated with corticosteroids and long-term immunosuppressive therapy, leading to complete resolution of intraocular inflammation. Final visual acuity was 20/30 at one year of follow up.ConclusionsSympathetic Ophthalmia following chemical ocular burns is extremely uncommon. It can present as a diagnostic and therapeutic challenge. It warrants early diagnosis and management.

Latent Mycobacterial fortuitum infection presenting as ocular sarcoidosis

A 62-year-old lady presented with bilateral granulomatous uveitis and cystoid macular edema. A diagnosis of ocular sarcoidosis was made (revised International Workshop on Ocular Sarcoidosis [IWOS] criteria) on the basis of lymphopenia, negative Mantoux, and QuantiFERON TB gold tests. Enlarged mediastinal lymph nodes, subpleural nodules, and nodular interstitial thickening were seen on high-resolution computed tomography (HRCT) thorax. Non-necrotizing granulomato us inflammation, negative for mycobacteria on staining and GeneXpert, was noted on endobronchial ultrasound-guided transbronchial lymph node aspiration (EBUS-TBNA). However, culture grew Mycobacterium fortuitum after 3 weeks. This case highlights a rare presentation of latent M. fortuitum infection presenting as ocular sarcoidosis, speculating the coexistence of two diseases in an individual, one possibly triggering the other.

Identification of immune hub genes participating in the pathogenesis and progression of Vogt-Koyanagi-Harada disease.

BackgroundVogt-Koyanagi-Harada (VKH) disease is an autoimmune inflammatory disorder characterized by bilateral granulomatous uveitis. The objective of this study was to identify immune hub genes involved in the pathogenesis and progression of VKH disease.MethodsHigh throughput sequencing data were downloaded from the Gene Expression Omnibus (GEO) and an immune dataset was downloaded from ImmPort. Immune differentially expressed genes (DEGs) were obtained from their intersection in the GEO and ImmPort datasets. Immune hub genes for VKH disease were selected through differential expression analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO), protein-protein interaction (PPI) network, and clustering analyses. Confidence in the immune hub genes was subsequently validated using box plots and receiver operating characteristic (ROC) curves.ResultsA total of 254 DEGs were screened and after the intersection with ImmPort, 20 genes were obtained as immune DEGs. Functional enrichment analysis indicated that the key genes were mainly involved in several types of immune pathways (such as the lymphocyte mediated and leukocyte mediated immune responses, natural killer cell mediated cytotoxicity, and antigen binding) and immunodeficiency diseases. Following PPI network analysis, the top seven genes in cluster 1 were selected as potential immune hub genes in VKH. After evaluating the accuracy of the hub genes, one gene (GNLY) was excluded because its expression level was statistically similar in VKH patients and healthy controls. Finally, six immune hub genes, namely KLRC2, KLRC3 SH2D1B, GZMB, KIR2DL3, and KIR3DL2 were identified as playing important roles in the occurrence and development of VKH disease.ConclusionSix immune hub genes (KLRC2, KLRC3 SH2D1B, GZMB, KIR2DL3, and KIR3DL2) identified by our bioinformatics analyses may provide new diagnostic and therapeutic targets for VKH disease.

Sympathetic Ophthalmia: An Overview

Sympathetic ophthalmia (SO) is a bilateral granulomatous uveitis following penetrating ocular trauma or surgery. It is a rare but important cause of irreversible visual loss in trauma. Early identification and intervention is therefore vital in mitigating the long term effects of this potentially sight threatening disease.

Rare ocular manifestation of papilledema and bilateral choroidal tubercles in disseminated miliary tuberculosis

An 11-year-old female on treatment for miliary tuberculosis presented with decreased vision. Examination revealed bilateral disc edema, granulomatous uveitis, and multiple choroidal tubercles. Oral steroids were added. She was lost to follow-up, and 3 months later she had further visual loss due to optic atrophy. Repeat imaging of the CNS showed regression of the brain parenchymal lesions. This is a rare presentation of ocular tuberculosis in the setting of disseminated TB. While the mainstay of therapy is antitubercular therapy, this case highlights the importance of systemic corticosteroids to decrease both ocular and CNS inflammation and halt further vision loss.

Recent advances in diagnosis and management of sympathetic ophthalmia.

Sympathetic ophthalmia is a bilateral granulomatous uveitis that occurs following unilateral trauma or surgery and is sight-threatening in the contralateral eye. Despite significant potential morbidity, disease remains poorly understood. Variable presentations and clinical courses, as well as a lack of definitive diagnostic laboratory tests can complicate the diagnosis and result in delayed treatment, which can beget permanent vision loss. This review focuses on recent advances in areas of pathophysiology, classification, diagnosis and treatment. Sympathetic ophthalmia is thought to involve a cell-mediated immune response to retinal and uveal antigens exposed through trauma or surgery. Multiple mechanisms have been implicated, including activation of the interleukin-23/IL-17 pathway. Ongoing emphasis is placed on early disease recognition and prompt treatment with multimodal imaging. Multiple authors advocate for the routine use of optical coherence tomography (OCT) for screening and disease monitoring. Systemic steroids and steroids sparing-immunosuppressive agents remain the mainstay of treatment. Understanding pathophysiology may provide useful targets for drug development, as well as allow for identification of patients at risk. OCT is a useful tool in early diagnosis and management of sympathetic ophthalmia, as OCT changes may precede clinical symptoms and signs, allowing for early disease detection and better visual outcomes.

Case Report: Co-existence of sarcoidosis and Takayasu arteritis

Takayasu arteritis is a rare systemic large vessel vasculitis affecting the aorta and its branches. Sarcoidosis, too, is an inflammatory disease. Both entities are granulomatous conditions with a question of possible linkquestionable association in their etiopathogenesis. Only a few cases of their coexistence have been reported in the literature. To our knowledge, no such cases have been reported from Nepal. We report a Nepalese woman who presented with non-productive cough, progressive shortness of breath and chest tightness of 3 years duration. She had a history of recurrent bilateral granulomatous uveitis over the previous 3 years. Examination revealed clubbing of digits, absent pulses over the left radial, ulnar and brachial arteries, and a weak pulse over the right arm including the bilateral carotid arteries. Pulmonary function test showed restrictive pattern, a high-resolution computed tomography (HRCT) scan of the chest revealed findings suggestive of pulmonary sarcoidosis. A CT aortogram suggested large vessel vasculitis. Bronchoscopy with biopsy revealed granulomatous inflammation, negative for malignancy and tuberculosis. She was hence, diagnosed with co-existing Takayasu arteritis and sarcoidosis, and treated with Prednisolone 60 mg once daily with dramatic improvement over 4 days and was discharged stable on domiciliary oxygen. She is currently on azathioprine 50 mg, prednisolone 10 mg without the need for supplemental oxygen. This case report highlights the importance of a proper physical examination as a guide to the use of modern technology in making a correct diagnosis. Furthermore, in countries where tuberculosis is endemic, it should always come as the most important differential diagnosis of granulomatous inflammation.

P165 New relevant associations with vogt-koyanagi-disease (VKH) were found in Mexicans, using NGS technology. A new allele at DPA1 locus was detected in a VKH patient

Aim VKH is a systemic autoimmune disorder affecting tissues containing melanin, mainly the eyes. It is characterized by severe bilateral granulomatous uveitis. VKH is a T cell mediated disease vs. specific auto-antigens relevant in its pathogenesis. We and others showed that a shared epitope in the first DRB1 domain is clearly associated with VKH. DRB1*04:05 and 04:04 are strongly involved in Mexicans and other contributing DRB1 alleles, were also published by us: DRB1*04:05> *04:04 > *04:07 > *01:01 > *01:02. We now explored the whole MHC region, to unravel the complete MHC genetics of VKH. Methods We selected 77 unrelated donors from Mexico City and 49 VKH patients from the APEC. DNA samples were extracted in the Maxwell 16 instrument. For HLA typing, the MIA FORA NGS FLEX HLA Kit (Immucor, Inc) and The Illumina MiSeq, were used. Sequence analysis was performed with the Mia Fora software. Genotypes were assigned at all loci unambiguously, except for DPB1. Allele and haplotype frequencies (AF/HF) were done with the Arlequin, PyPop and Hapl-o-Mat v.1.1 software. Results A hierarchy of Class I/class II associations were found with deep sequencing: DQB1*03:02:01 (p = 0.000007); DQA1*03:01:01(p = 0.0002); C*03:04:01 (p = 0.007); DRB1*04:04:01(p = 0.005); DRB1 *04:07:01 (p = 0.01); DRB1*04:05:01; (p = 0.02); B*48:01:01 (p = 0.04); A*68:01:01(p = 0.02); DPB1 *03:01:01(p = 0.02). The OR was between 2.9 and 7.3. Amerindian (AMI), Hispanic and Asian alleles are evident at all loci. The most frequent haplotype in VKH is of Mexican AMI descent : A*02:01:01 B*39:05:01 C*07:02:01 DRB1*04:07:01

Tuberculous Uveitis Presenting with a Bullous Exudative Retinal Detachment: A Case Report and Systematic Literature Review

ABSTRACTPurpose: To describe tuberculous uveitis (TU) presenting as a bullous retinal detachment (RD) and to perform a comprehensive literature review on TU with similar features.Methods: Observational case report and systematic literature review.Results: An 84-year-old woman presented with bilateral granulomatous uveitis and bullous RD in the left eye. The interferon gamma release assay was strongly positive, but all other tests were unremarkable. The patient was diagnosed with TU and started on anti-tubercular therapy (ATT) and systemic steroids with excellent treatment response. Twenty-six articles (32 cases) reported TU with exudative RD. Choroidal tuberculoma was the most common clinical manifestation, followed by optic disc edema and retinal exudate. Systemic steroids with ATT improved vision in more patients (78.6%) than ATT alone (50.0%) or oral steroids followed by ATT (50.0%).Conclusion: Atypical presentations of TU make diagnosis and treatment difficult. A high level of suspicion for TU is needed to minimize ocular morbidity.

Ocular Involvement in Sarcoidosis.

AbstractOcular involvement in sarcoidosis occurs in ∼40% and the eye is the presenting organ in roughly 20%. The course of ocular disease does not necessarily parallel that of systemic disease. Uveitis is the most common presentation and shows mainly a chronic course; anterior uveitis is associated with better visual prognosis than posterior localization. Painful bilateral anterior granulomatous uveitis most commonly occurs in black patients at younger age, while painless posterior bilateral involvement with peripheral multifocal choroiditis is commonly seen in elderly white females. Patients with posterior uveitis develop often ocular complications and central nervous system involvement. Vitritis, segmental periphlebitis, choroidal granulomas, and peripheral multifocal chorioretinitis are often seen clinical features. Optic nerve involvement is uncommon, but if present, results often in poor visual outcome. Lacrimal gland and conjunctival involvement are also common and present clinically as dry eyes or remain asymptomatic with good visual prognosis. Sarcoidosis-associated uveitis is mostly managed by local treatment with steroid drops or periocular and intraocular steroid injections or with novel intraocular corticosteroid implants. Patients with sight-threatening disease or optic nerve involvement need systemic therapy. Systemic therapy is based on a step-up regimen where corticosteroids are used in the initial phase of the disease and if long-term treatment is required, steroid-sparing immunomodulatory drugs are implemented such as methotrexate or biological agents. Despite the mainly chronic course, need for long-term treatment, and frequent ocular surgeries in the majority of patients, the visual outcome of sarcoidosis-associated uveitis is fairly good if therapy has started on time.

Ocular sarcoidosis

Ocular manifestation of sarcoidosis occurs in up to 60% of patients with confirmed systemic sarcoidosis and represents one of the most common forms of noninfectious uveitis. In known pulmonary sarcoidosis, ocular involvement can occur in up to 80% of cases. Sarcoidosis can also present only in the eye, without asystemic manifestation (ocular sarcoidosis). Typically, ocular sarcoidosis shows bilateral granulomatous uveitis and can involve all parts of the eye. Apart from an acute anterior uveitis, chronic intermediate or posterior uveitis can be found. In order to prevent asevere reduction of visual acuity leading to blindness, early diagnosis and treatment is essential. For diagnosis, specific clinical signs involving the eye (bilateral granulomatous changes in all parts of the eye) and typical laboratory investigations (angiotensin-converting enzyme, ACE; lysozyme; soluble interleukin2 receptor, sIL2R; chest X‑ray; chest CT) have to be taken into account, since biopsy to prove noncaseating granulomas is not performed with changes restricted to the eye due to the high risk of vision loss. Ocular sarcoidosis mostly responds well to local or systemic steroid treatment. If the therapeutic effect is insufficient, immunosuppressive agents and biologics can be applied.

Recurrent sympathetic ophthalmitis

Sympathetic ophthalmitis (SO) is a rare, bilateral granulomatous uveitis occurring after perforating eye injury or ocular surgical procedure to one eye. The pathophysiology of this entity is not clearly understood, but an autoimmune hypersensitivity reaction against exposed ocular antigens in the injured eye is believed to be responsible for this disease. In this article, we present a patient with clinical diagnosis of SO with it recurrence.

Bilateral congenital cataract with suspected lens-induced granulomatous uveitis

A healthy newborn baby girl presented with congenital bilateral cataract. Within a few days of presenting she also developed bilateral granulomatous uveitis, a condition generally linked in newborns to congenital infections, most frequently TORCHES syndrome (toxoplasmosis, rubella, cytomegalic inclusion disease, herpesvirus, including Epstein-Barr, syphilis). Extensive investigation did not reveal any underlying etiologic mechanism. Treatment with topical and systemic steroids did not improve the uveitis. However, bilateral lens extraction resulted in a quick resolution of the uveitis.

Diagnostic perspectives and treatment efficacy in the Vogt-Koyanagi-Harada disease

Vogt-Koyanagi-Harada (VKH) disease should be part of the differential diagnosis of a bilateral granulomatous uveitis. VKH is more common in the Mongoloid race (most frequently in Japanese, American Indians), and people of Hispanic descent. In Europeans, it is rare; mostly in women aged 30-50 with dark skin and hair pigmentation. The prodromal stage of VKH disease is non-specific but may include headache, vomiting and general malaise. Indocyanine green angiography may be helpful in making the diagnosis. Presenting a clinical case, the authors discuss the methods for diagnosis and follow-up for patients with Vogt-Koyanagi-Harada disease. Effective and timely treatment with high dose corticosteroids, if necessary in combination with immunosuppression, could save good visual functions.

한양방 동시치료로 호전된 추정 보그트-고야나기-하라다병 증례

Vogt-Koyanagi-Harada(VKH) Disease is a bilateral granulomatous uveitis often associated with exudative retinal detachment and extraocular manifestations, such as pleocytosis in the cerebrospinal fluid and, in some case, vitiligo, poliosis, alopecia, and dysacusis. There has been no previous report for the disease in the field of Korean traditional medicine. The case was treated with conventional medical intervention and Korean traditional treatment including acupuncture and herbal medicine. The case was discharged with improvement in fundus photography and optical coherence tomography. The authors report the case to suggest that Korean medical approach combined with conventional treatment can be helpful for the disease.

A Case of Neurosyphilis Revealed by Acute Exudative Polymorphous Vitelliform Maculopathy

The authors report the case of a healthy 56-year-old man presenting with bilateral vision loss. Clinical features were consistent with the diagnosis of acute exudative polymorphous vitelliform maculopathy (AEPVM). The patient returned 10 days later with bilateral anterior granulomatous uveitis, and the inflammatory work-up revealed treponemal antibodies in the serum and spinal fluid, consistent with a diagnosis of active neurosyphilis. The patient received standard treatment for neurosyphilis with intravenous penicillin G. Two months later, the intraocular inflammation had resolved, but the resolution of the vitelliform lesions was more gradual. An immune process could be a plausible explanation for these clinical findings. Clinicians should be aware that syphilis can produce AEPVM.