The prevalence of human papillomavirus in ocular surface squamous neoplasia in HIV positive and negative patients in a South African population.

PURPOSE: To assess the prevalence and subtypes of Human Papillomavirus (HPV) in Ocular Surface Squamous Neoplasia (OSSN) in Human Immunodeficiency Virus (HIV) positive and negative patients in South Africa. BASIC PROCEDURES: This study was a single center retrospective cross-sectional study, conducted at Tygerberg Hospital, Western Cape, South Africa. We assessed 63 histopathologically confirmed OSSN formalin-fixed paraffin-embedded (FFPE) tissue blocks from 2015-2023. The presence of HPV was determined using the Hybrispot Direct Flow Chip Kit. Corresponding clinical data was retrieved from the National Health Laboratory Service (NHLS) central data warehouse. MAIN FINDINGS: Of the confirmed OSSN samples, 66.7% tested positive for HPV (95% confidence interval [CI] 54-77.3%). Of the 42 HPV positive samples, 38 (90.5%) had one or more known genotypes detected and 4 had unknown genotypes. The most prevalent subtypes were HPV 11, 16 and 18 (found in 61.9%, 52.4% and 33.3% of HPV positive samples respectively). 88.9% of the lesions biopsied were from HIV positive patients, of whom 56.4% had a CD4 + count of < 200 cells/µL. A lower median CD4 + count was detected among HIV positive patients with invasive squamous cell carcinoma compared to those with moderate dysplasia (p < 0.0198). CONCLUSIONS: There is a high prevalence of HPV in OSSN in South Africa. Certain subtypes namely, 11, 16, 18, 31, 33 and 35 may be more carcinogenic. HIV with HPV co-infection may be linked as a causative factor in the development of OSSN.

Evaluation of Potential Antigen-specific Host Biomarkers in QuantiFERON Supernatants as Candidates for the Diagnosis of Ocular Tuberculosis.

Purpose: To evaluate potential host biomarkers detectable in QuantiFERON supernatants as diagnostic candidates for ocular tuberculosis (OTB).Methods: We investigated 47 host markers in QuantiFERON supernatants from 92 individuals with uveitis using the Luminex platform. We evaluated the potential of individual and combined biomarkers to distinguish between patients with possible, probable, and no OTB.Results: Differences were observed in median concentrations of several biomarkers including IL-13, IFN-γ, IFN-α2, and IL-1ß, in individuals with OTB versus no OTB regardless of HIV status. Individuals with probable and possible OTB only differed regarding GM-CSF. We identified a four-marker biosignature (CD40 L, IL-33, IFN-γ, and SAP) which diagnosed OTB with an area under the ROC curve of 0.80, sensitivity = 56.3% and specificity = 90.0%.Conclusion: This represents the first attempt at screening QuantiFERON supernatants for biomarkers to diagnose OTB. We identified candidate biosignatures which may aid in diagnosing OTB in both HIV positive and negative patients.

Ocular Tuberculosis in HIV-infected Individuals.

Aim: To review the current literature and publications to assess the clinical features, recommended investigations and treatment for ocular tuberculosis in HIV infected patients. Methods: Literature review. Results: The human immunodeficiency virus (HIV) epidemic affects as many as 37.9 million people. Mycobacterium tuberculosis infection is common in HIV infection and is a leading cause of death and morbidity. Common clinical presentations include anterior uveitis (granulomatous or otherwise), choroidal granulomas/tubercles, chorioretinitis, subretinal abscess, panophthalmitis, retinal detachment and vasculitis. The majority of clinical findings were in the posterior segment, appeared primarily infective (tubercles/chorioretinitis/abscess) and were largely seen in the context of pulmonary tuberculosis or disseminated disease. Current investigational patterns include corroborative tests such as tuberculin skin test or Interferon-γ release assay. Systemic testing includes Computed Tomography, MRI or PET/CT scans. Newer Molecular techniques such as GeneXpert MTB/RIF assay and Line Probe assays (LPA) are increasingly important. Apart from standard ocular anti-inflammatory protocols, anti-tubercular treatment as per the clinical staging (latent or active) needs to be initiated. Initiation of anti-retroviral therapy (ART) is important and can be started soon after ATT. Conclusions: Ocular manifestations within this group are distinct and unique investigational and therapeutic approaches are needed.

Eyelid and Orbital Involvement in HIV Infection - An African Perspective.

Both infective and neoplastic eyelid and orbital conditions in human immunodeficiency virus (HIV) infected patients are often the result of opportunistic or co-infections (OI). In most cases, these clinical findings in younger patients alert the physician to suspected underlying HIV infection. When the eyelids and periorbital skin are primarily involved in OI with varicella-zoster virus it is called Herpes Zoster Ophthalmicus. Co-infection with a Pox virus manifests as molluscum contagiosum eruptions. Orbital cellulitis is secondary to various organisms (Mycobacterium tuberculosis, Candida albicans, Aspergillus). Neoplastic disorders are also often associated with OI such as human herpes virus 8 in Kaposi Sarcoma, Epstein-Barr virus in Hodgkin Lymphoma and human papillomavirus 16 and 18 in squamous cell carcinoma. In this review we share our personal clinical experience with HIV disease in Sub-Saharan Africa over more than two decades and provide photographs of cases to illustrate pertinent aspects of the conditions discussed.

The Etiology of Intraocular Inflammation in HIV Positive and HIV Negative Adults at a Tertiary Hospital in Cape Town, South Africa.

PURPOSE: To describe the patterns of uveitis in South Africa. METHODS: Prospective cross-sectional study. RESULTS: One hundred and six patients were enrolled and 37.7% had human immune-deficiency virus (HIV) infection. Anterior and panuveitis occurred most frequently. Infectious, non-infectious and idiopathic uveitis were diagnosed in 66.0%, 17.0% and 17.0% of all cases, respectively. Eighty percent of HIV+ cases had infectious uveitis. Overall, intraocular tuberculosis (IOTB), herpetic and syphilitic uveitis were the commonest infectious causes. Sarcoidosis and HLA-B27-associated uveitis were the commonest non-infectious causes. In anterior uveitis, HIV+ cases most frequently had probable IOTB, syphilitic or idiopathic uveitis while HIV- cases had possible IOTB, idiopathic or HLA-B27-associated uveitis. In panuveitis, HIV+ cases mostly had syphilis, probable IOTB, toxoplasma and varicella-zoster virus whereas HIV- cases mostly had possible IOTB, sarcoidosis and idiopathic uveitis. CONCLUSION: Infectious uveitis is common in South Africa, especially amongst HIV+ patients. Causes of anterior and panuveitis differ between HIV+ and HIV- patients.

Polymerase Chain Reaction and Goldmann-Witmer Coefficient Testing in the Diagnosis of Infectious Uveitis in HIV-Positive and HIV-Negative Patients in South Africa.

PURPOSE: To use polymerase chain reaction (PCR) and Goldmann-Witmer coefficient (GWC) calculation to diagnose infectious uveitis. METHODS: Prospective cross-sectional study. RESULTS: Twenty-seven of 106 patients had positive PCR and/or GWC results on aqueous humor (AH) sampling and 15 of 27 (55.6%) were HIV-positive. Patients with non-anterior uveitis (NAU) were more likely to be HIV+ (p = 0.005). More than 1 possible pathogen was identified in 9 of 27 patients of whom 7 were HIV+. The final clinical diagnosis was discordant with AH findings in 9 of 27 cases. A positive EBV PCR result was associated with a discordant diagnosis (p = 0.001). All cases of herpetic anterior uveitis (42.9% HIV+) tested PCR-/GWC+ while all cases of herpetic NAU tested PCR+/GWC- (83.3% HIV+). All rubella virus cases were PCR+/GWC+. CONCLUSION: PCR is useful to diagnose herpetic NAU in HIV+ patients while GWC is useful to diagnose herpetic anterior uveitis.

The Role of QuantiFERON®-TB Gold and Tuberculin Skin Test as Diagnostic Tests for Intraocular Tuberculosis in HIV-Positive and HIV-Negative Patients in South Africa.

PURPOSE: To compare QuantiFERON®-TB Gold and tuberculin skin testing as diagnostic tests for intraocular tuberculosis in HIV positive and negative patients. METHODS: A prospective study evaluating two different tests to help diagnose intraocular tuberculosis. RESULTS: Thirty-five of 106 patients (33.0%) were diagnosed with intraocular tuberculosis including 11 (31.4%) with HIV infection. Patients were 6.95 times more likely to have intraocular tuberculosis if TST alone was positive (p < 0.001) versus 2.19 times more likely if Quantiferon alone was positive (p = 0.04). Tuberculin skin testing showed superior specificity (60.3% vs 33.3%) (p = 0.001) but similar sensitivity (90.3% vs 85.7%), positive (54.9% vs 40.5%) and negative predictive values (92.1% vs 81.5%) compared to Quantiferon. Specificity did not increase significantly if both skin testing and Quantiferon were positive. CONCLUSIONS: In South Africa, with its high HIV burden and limited public health resources, Quantiferon testing should not replace tuberculin skin testing as it provides little additional diagnostic information.

Recurrent Pulmonary Aneurysms: Hughes-Stovin Syndrome on the Spectrum of Behçet Disease.

In this report, we describe a male patient who presented with recurrent life-threatening hemoptysis due to the sequential formation of multiple pulmonary aneurysms. Both pulmonary artery coil embolization and right lower lobectomy were performed, with limited success. The patient experienced extensive bilateral femoral DVT extending into the inferior vena cava, with massive hemoptysis, fulfilling the diagnosis of Hughes-Stovin syndrome. A final diagnosis of Behçet disease was made following extensive investigation, and the patient responded well to prednisone 20 mg orally and azathioprine 100 mg orally.

Intralesional bleomycin for the treatment of periocular capillary hemangiomas.

Periocular infantile capillary hemangiomas do not always respond well to conventional treatment modalities such as systemic or intralesional corticosteroids, radiotherapy or debulking surgery. The authors describe the use of intralesional bleomycin injections (IBIs) to treat potentially amblyogenic lesions in two cases where other modalities have failed. In both cases monthly IBIs successfully cleared the visual axis of the affected eye before the age of 1 year thus preventing permanent sensory deprivation amblyopia. A total of five and nine injections, respectively, were used and no significant side effects were noted. IBI appears to be a useful alternative in the treatment of periocular capillary hemangiomas refractory to more conventional modalities.