Ophthalmologic peculiarities of sarcoidosis

The present paper deals with the frequency of different ophthalmic sarcoid changes and their morphological and photographic characteristics. In addition, the diagnostic value of conjunctival biopsy is evaluated. The findings were based on repeated ophthalmological examinations of an unselected group of 281 patients with histologically confirmed sarcoidosis. Conjunctival (37/218) and lacrimal gland (33/254) changes were encountered more often than sarcoid uveitis (22/281), and a conjunctival granuloma was the most frequent single sarcoid ophthalmic finding. Sarcoid changes in the eyes and the adnexae were often characterized by a scarcity of symptoms and a typical outward appearance. In some cases of sarcoid uveitis fluorescein angiography revealed in the iris and the retina nodules which showed features suggesting the proliferative nature of the disease. The iris infrared transillumination technique illustrated the affinity of sarcoid nodules in the pupillary area. Conjunctival biopsy showed epithelioid cell granulomas compatible with sarcoidosis in nearly half of the patients in whom it was suspected in a slit-lamp examination of the conjunctivae. In the diagnosis of sarcoidosis, conjunctival biopsy is a procedure to be recommended before more demanding methods are tried.     

Pyogenic granulomas

Four cases of conjunctival pyogenic granuloma are described. The patients ranged in age from 12-30 years. Surgical trauma preceded the development of two lesions in one patient and a second patient presented with a positive history of recurrent styes, a chalazion, and a questionable history of trauma to the lid. The other two patients had no known antecedent events that would explain development of the lesions. A review of the literature is included in the discussion, which details the etiology, incidence, clinical presentation, histopathology, symptoms, clinical course, differential diagnosis, and treatment of pyogenic granulomas.     

Phenotypes of conjunctival inflammatory cells in sarcoidosis.

Phenotypes of the infiltrating mononuclear cells of the lower fornix conjunctiva of nine patients with sarcoidosis and six controls were studied using monoclonal antibodies and a modified immunoperoxidase method. Four patients had sarcoidosis of recent onset (duration of 2 years or less) and five patients had a chronic disease (duration of 3 or more years). The inflammatory cells in the sarcoid conjunctival specimens were predominantly T lymphocytes, the vast majority of which were of T helper/inducer subtype expressing Leu-3a + 3b positivity. The ratio of T helper/inducer cells to T suppressor/cytotoxic cells was 3.9 on average but only 0.9 in controls. Epithelioid cell granulomas were seen in three specimens in one case of recent onset and in two chronic cases comprising a marked amount (more than 15 cells/visual field) of cells bearing phenotypes of macrophages, T cells, T helper/inducer cells and HLA-DR antigen, and in smaller quantities of T suppressor/cytotoxic cells. The mean number of all immunocompetent cell subtypes of specimens from newly diagnosed patients exceeded that of specimens from chronic patients. We believe that the sarcoid immune reaction in the conjunctiva is a dynamic process in which proliferation of immunocompetent mononuclear cells precedes the stage of granuloma formation.     

Whole-body 18FDG PET-CT Imaging of Systemic Sarcoidosis: Ophthalmic Oncology and Uveitis

Purpose: To describe whole-body 18-fluorodeoxyglucose (FDG) positron emission tomography/computed radiographic tomography (PET-CT) imaging of ophthalmic patients with systemic sarcoidosis. Methods: Four systemic sarcoidosis patients were evaluated with PET-CT for staging. Two had been treated for conjunctival melanoma and two had been referred for atypical choroidal tumors. PET-CT images were studied for presence of tumor or tissue with increased standardized uptake values, indicating increased metabolic activity. Results: In all cases, PET-CT revealed focal systemic lesions with increased uptake (SUV range 1.7–5.9 kg/mL). Cases 1 and 2 had a previous diagnosis of sarcoidosis (without ocular involvement), while cases 3 and 4 were diagnosed during their work-up. PET-CT revealed the presence and distribution of systemic sarcoid granulomas. Conclusions: In this series, PET-CT staged patients with eye cancer and systemic sarcoidosis and aided in differentiating between a metastatic choroidal tumor and uveal sarcoid granuloma. PET-CT offers a method to assess the presence and distribution of systemic sarcoidosis.     

Conjunctival pyogenic granuloma in a patient with chalazions

A 28-year-old male patient had a chalazion on his left eyelid. Increased discomfort led to the discovery of a conjunctival mass under the inner part of his upper eyelid. On clinical examination, a small reddish mass on the palpebral conjunctiva of the upper left eyelid was only visible on the underside of the lid; the mass was diffusely reddish. Additionally, a chalazion was present in the middle of the lower left eyelid. As this condition was a source of discomfort to the patient, the mass was surgically resected. The histological study found a typical pyogenic granuloma, a possible complication in the course of a chalazion.     

ACE2 and TMPRSS2 are expressed on the human ocular surface,suggesting susceptibility to SARS-CoV-2 infection

PurposeConjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection.MethodsWe analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2.ResultsAcross all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as weak or focal expression in the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, Western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2.ConclusionsTogether, these results suggest that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.     

Ocular rosacea. A histologic and immunopathologic study

Acne rosacea is an idiopathic dermatologic disease that frequently produces conjunctival inflammation. The authors studied the histology and immunopathology of epibulbar conjunctival biopsy specimens from eight patients with ocular rosacea and compared the findings with those from conjunctiva from 13 normal individuals. The conjunctival epithelium in ocular rosacea was attenuated and infiltrated by inflammatory cells, mainly T-helper/inducer (CD4) cells, phagocytic cells, and antigen-presenting (CD14, Mac-1) cells. The difference between the normal control group and the rosacea group in the number of mononuclear cells forming these populations was statistically significant (P less than 0.01). The substantia propria of the rosacea specimens contained large subepithelial infiltrates of chronic inflammatory cells, and in some cases frank granuloma formation was evident. There was an overall mean increase of nearly all cell types, but especially of T-helper cells in the rosacea specimens compared with the controls. Interestingly, T-helper/inducer (CD4) cells, which were outnumbered by the T-suppressor (CD8) cells in the normal conjunctival epithelium (CD4/CD8 = 0.85), outnumbered the CD8-positive cells in the rosacea specimens (CD4/CD8 = 1.6). There also was a 3.5-fold increase of the CD4/CD8 ratio in the rosacea conjunctival stroma compared with the normal specimens. The mechanism involved in rosacea conjunctival inflammation resembles a type IV hypersensitivity reaction.     

Conjunctival lymphocyte subsets in trachoma

Monoclonal antibodies were used to assess the lymphocyte populations in conjunctival biopsy specimens obtained from patients with trachoma (active or inactive) undergoing tarsotomy for the correction of trachoma-induced entropion and in three control patients. Peroxidase-labelled monoclonal antibodies OKT4 (identifies T-helper/inducer lymphocytes), OKT8 (identifies T-suppressor/cytotoxic lymphocytes), OKIal (identifies B-lymphocytes) and antisera specific for IgG, IgA and IgM were used to identify lymphocyte subpopulations and immunoglobulins in the conjunctival biopsy specimens. When grouped by disease activity, conjunctival tissue specimens revealed predominant T-helper/inducer lymphocytes in the substantia propria of patients with active trachoma while inactive trachoma patients had predominant T-suppressor/ cytotoxic lymphocytes in the conjunctival biopsy specimens. B-lymphocytes were seen in moderate numbers in all conjunctival biopsy specimens from patients with active trachoma and all specimens from active cases stained for IgG, IgM, and IgA. Immunoglobulin staining was strongest with IgG and IgM.     

Pyogenic granuloma as a presenting sign of hydroxyapatite orbital implant exposure: a clinicopathologic study

PURPOSE: We report 5 unusual cases of exposed hydroxyapatite orbital implants that presented as pyogenic granulomas. We propose pathogenesis and histopathologic correlations. METHODS: A clinicopathologic study of 5 patients with hydroxyapatite implants who presented with pyogenic granuloma. RESULTS: Pyogenic granulomas were detected 1.5 to 30 months after implantation in 5 patients. The lesions were multiple but were not related to the wound margin at the exposed area and were not covered by the surface epithelium in most instances. Exposure defects were detected in all patients at the time of lesion excision. The mean exposure size in the greatest dimension was 16 mm (range, 9-20 mm). Three patients were treated successfully with simple excision of the granulomas, burring down of the anterior surface of the implants, and direct repair of the exposure defects. Explantation of the implant was performed in 2 cases. Histopathologic examination revealed chronic inflammation and microabscess formation in the explanted implants. CONCLUSIONS: Five patients with pyogenic granulomas were found to have hydroxyapatite exposure. Pyogenic granuloma should not be considered a benign lesion on a hydroxyapatite orbital implant, especially in recurrent cases. Ophthalmologists must be aware of the possibility of conjunctival dehiscence with hydroxyapatite-implant exposure beneath the lesion.     

Angiotensin-converting enzyme in sarcoid uveitis.

The diagnosis of ocular sarcoid is presumptive in the absence of systemic disease. The association of elevated serum angiotensin-converting enzyme (ACE) levels with active systemic sarcoid has been well described. With a sensitive fluorimetric assay for ACE, we found that five of ten chronic granulomatous uveitis patients without systemic sarcoid had elevated serum ACE levels. None of ten patients with uveitis of known etiology had elevated serum ACE levels. We believe that the association of an elevated serum ACE level with chronic granulomatous uveitis suggests the diagnosis of ocular sarcoid.     

Conjunctival deposits as an initial manifestation of sarcoidosis.

PURPOSE: To report conjunctival deposits as an initial manifestation of sarcoidosis. METHODS: Case reports. RESULTS: Two patients with bilateral bulbar conjunctival white deposits underwent conjunctival biopsy. The biopsy specimens showed noncaseating granulomas with prominent Schaumann bodies. Serum angiotensin-converting enzyme levels were increased in both patients. The first patient had abnormal results of pulmonary function tests. Sarcoidosis was diagnosed in both patients. CONCLUSIONS: Conjunctival deposits may represent the initial clinical manifestation of sarcoidosis.     

Conjunctival Granulomas Caused by Synthetic Fibers: Report of Two Cases and Review of Literature

PURPOSE: We sought to demonstrate the histopathologic and ultrastructural features of conjunctival foreign body granulomas because of synthetic fibers and to compare them to other cases published in the literature. METHODS: A 2- and a 7-year-old girl were referred for the surgical removal of slow-growing unilateral inferior conjunctival masses with a lack of primary trauma or surgery. In this report, we describe the light and electron microscopic findings of the 2 cases and review the literature of similar cases using the Medline database. RESULTS: Histopathologic and ultrastructural examination of both specimens revealed a granulomatous inflammatory cell response, including histiocytes and multinucleated foreign body giant cells around acellular, uniform sized, oval to round birefringent fibers with manufacturing artifacts. Thirteen other patients with conjunctival synthetic fiber granulomas were identified from the literature. CONCLUSIONS: On the basis of the findings in our cases and the review of literature, it appears that conjunctival synthetic fiber granulomas are not a rare entity but are not recognized frequently by ophthalmologists. The most reliable clinical sign to suggest this diagnosis is the presence of a unilateral inferior conjunctival mass in a child or adolescent. Histopathologic and ultrastructural evaluation appears to be the only way to specifically diagnose this condition with certainty.     

Ophthalmologic disease in sarcoid-like granulomatosis and true sarcoidosis in immunodeficiency. Four case reports

Granulomatosis lesions occurring after diagnosis of primary or secondary immunodeficiency are not accidental and have been described in a small number of patients suffering from various diseases: common variable immunodeficiency (CVID), malignancy (lymphoma and solid tumors), and acquired immunodeficiency syndrome (AIDS). Two types of granulomatosis can appear: true sarcoidosis and sarcoid-like reaction. We report four patients, two with CVID and two with malignancy, in whom clinical granulomatosis appeared a few months to a few years after diagnosis of immunodeficiency. They developed noncaseating granulomas of the lung, spleen and liver associated with conjunctival granulomas and bilateral panuveitis. The granulomatous disorder was diagnosed after immunodeficiency on histopathological studies revealing noncaseating granulomas. Causation agents such as infectious organisms and environmental compounds were excluded. The relationship between sarcoid-like reaction, true sarcoidosis and immunodeficiency is discussed. The underlying pathophysiology responsible for the association between granuloma formation and immunodeficiency in the same patient remains obscure. It may be quite difficult to distinguish true sarcoidosis and sarcoid-like reaction. It is possible that these two entities are the clinical extremes of a common pathological process.     

Assessment of activity of ocular sarcoidosis by gallium scanning.

Gallium (67Ga) citrate uptake over the orbits, parotid glands, and lungs was examined in six newly detected patients with sarcoidosis and 17 with chronic sarcoidosis. Six of 23 (26%) had uveitis, 18/23 (78%) decreased lacrimal secretion, and 13/16 (81%) epithelioid cell granulomas in conjunctival biopsies. Ten patients with other diseases served as controls. Only five patients had ocular complaints and two had enlarged parotid glands. 67Ga uptake over the orbits and parotids was measured by a quantitative computer based method. Gallium uptake was significantly higher over the orbits (p less than 0.001) and parotids (p less than 0.01) in the newly detected patients and in the parotids (p less than 0.01) in the chronic group than the corresponding uptake in the controls. We suggest that in sarcoidosis an increased 67Ga uptake in the orbital and parotid areas may be a phenomenon comparable to an increased 67Ga uptake in the lungs in active alveolitis. Gallium scan is a good method for revealing even symptomless ophthalmic sarcoid changes. However, in chronic sarcoidosis an equal or only slightly increased gallium uptake over the orbits compared with background activity does not exclude ocular sarcoid disease.     

The contribution of inflammatory cell infiltration to conjunctival inclusion cyst formation

PURPOSE: The incidence of inclusion cysts was examined histopathologically in conjunctival disorders where inflammatory cell infiltration was seen in the subepithelial connective tissue. METHOD: The incidence of inclusion cysts was examined histopathologically in pterygium, vernal conjunctivitis, pyogenic granuloma and pingueculitis. The specimens of pinguecula were used as control. RESULTS: Inclusion cysts were recognized in 5/55 cases of pterygium, 2/12 cases of vernal conjunctivitis, 1/4 cases of pyogenic granuloma, and 1/2 cases of pingueculitis. On the other hand no inclusion cyst was recognized in 20 cases of pinguecula in which no inflammatory cell infiltration was seen. CONCLUSIONS: Inflammatory cell infiltration may contribute to the formation of conjunctival inclusion cysts in pterygium, pingueculitis, vernal conjunctivitis and pyogenic granuloma.     

Course and outcome of ocular sarcoidosis

In a series of 281 patients with histologically confirmed sarcoidosis, 79 initially had ophthalmic sarcoid manifestations. Of 22 patients with uveitis, 21 were seen regularly as long as the inflammation was active, and 71 of the 79 patients (90%) underwent a follow-up study five to 16 years (mean, nine years) later and using the same protocol. In the 21 patients with uveitis, the disease exhibited either a monophasic course (eight patients) with favorable visual outcome or a relapsing course (13 patients) with severe visual loss in five eyes. Thirty-three patients showed chronic ophthalmic changes at the follow-up examination, including conjunctival granulomas (13 patients), lacrimal gland involvement (22 patients), uveitis (four patients), and involvement of lacrimal passages (three patients). In 15 of these 33 patients, the general physical examination and the chest x-ray showed no evidence of systemic sarcoidosis. However, the serum angiotensin converting enzyme level was increased in a significantly greater proportion of these 15 patients than in the patients assessed as totally recovered from sarcoidosis.     

Optical Coherence Tomography and Management of a Retinal Granuloma in Presumed Ocular Sarcoidosis

Purpose: To highlight the utility of EDI-OCT and periocular steroid administration for the treatment of a retinal granuloma due to presumed ocular sarcoidosis. Methods: Retrospective case-study of a single patient. Results: A 45-year-old African-American male with blurred vision in the right eye was found to have a macula-involving retinal granuloma. Laboratory, imaging, and clinical findings were consistent with a diagnosis of presumed ocular sarcoidosis. Optical coherence tomography (OCT) and fundus photographs were used to document granuloma evolution. Oral prednisone 60mg was initiated and tapered to 10mg within 2 months. Due to systemic side-effects and inadequate treatment response with prednisone, 5 sub-Tenon’s triamcinolone acetonide (PSTA) injections were then administered over 7 months, and oral prednisone was discontinued at 6 months. Conclusion: This case demonstrated marked granuloma regression occurring with improvement in visual acuity, highlighting the utility of OCT and PSTA in managing retinal sarcoid granulomas.     

The Contribution of Inflammatory Cell Infiltration to Conjunctival Inclusion Cyst Formation

Purpose: The incidence of inclusion cysts was examined histopathologically in conjunctival disorders where inflammatory cell infiltration was seen in the subepithelial connective tissue.Method: The incidence of inclusion cysts was examined histopathologically in pterygium, vernal conjunctivitis, pyogenic granuloma and pingueculitis. The specimens of pinguecula were used as control.Results: Inclusion cysts were recognized in 5/(55) cases of pterygium, 2/(12) cases of vernal conjunctivitis, 1/(4) cases of pyogenic granuloma, and 1/(2) cases of pingueculitis. On the other hand no inclusion cyst was recognized in 20 cases of pinguecula in which no inflammatory cell infiltration was seen.Conclusions: Inflammatory cell infiltration may contribute to the formation of conjunctival inclusion cysts in pterygium, pingueculitis, vernal conjunctivitis and pyogenic granuloma.     

白细胞介素-6在瞼板腺囊腫組識中的表達

目的 为观察睑板腺囊肿组织中白细胞介素-6(IL-6)的异常表达,探讨睑板腺囊肿的确切病因。方法 采用SABC免疫组织化学染色法,对42例睑板腺囊肿内容物中白细胞介素-6(IL-6)的分布与表达进行研究。结果 研究显示42例中30例呈阳性表达,12例阴性。结论 白细胞介素-6的异常表达与睑板腺囊肿发生关系密切。