Derrick Smit

Polymerase chain reaction to search for Herpes viruses in uveitic and healthy eyes: a South African perspective

OBJECTIVE To analyse aqueous polymerase chain reaction (PCR) results in patients diagnosed with undifferentiated uveitis and determine prevalence of herpesviridae in non-uveitic patients undergoing routine cataract extraction. DESIGN Retrospective comparative case series and prospective cross-sectional study. SUBJECTS 72 patients with idiopathic uveitis and 57 surgical patients. METHODS Diagnostic aqueous paracentesis with PCR testing for 6 herpes viridae in uveitic patients. Anterior chamber paracentesis immediately pre-operative in the prospective arm, with PCR testing. RESULTS In the retrospective review we had a 47.2% positive PCR yield. Data analysis revealed a statistically significant correlation between a positive yield and being HIV+ (p=0.018); between an EBV+ yield and being HIV+ (p= 0.026) and a CMV+ result and being HIV+ (p=0.032). Posterior uveitis (p=0.014) and symptoms <30 days (p= 0.0014) had a statistically significant yield. In the prospective arm of the study: all 57 patients were HIV- and all aqueous samples were negative for the 6 herpesviridae. CONCLUSION We recommend PCR testing for Herpesviridae as a safe second line test for patients with undifferentiated uveitis. We were unable to establish prevalence and suggest that the idea of a commensal herpes virus is unlikely if the blood-ocular barrier is intact.

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.

Pharmacological testing in Horner's syndrome - a new paradigm

For more than three decades, topical cocaine has been used to confirm the diagnosis and hydroxyamphetamine to localise the causative lesion in oculosympathetic palsy or Horners syndrome. More recently, other drugs have demonstrated the ability to point to the diagnosis or anatomical site. Apraclonidine and phenylephrine, given their similar diagnostic efficacy and increased availability, may have superseded cocaine and hydroxyamphetamine as first-line pharmacological testing agents in Horners syndrome.

Polymerase Chain Reaction and Goldmann-Witmer Coefficient to Examine the Role of Epstein-Barr Virus in Uveitis

ABSTRACT Purpose: To use polymerase chain reaction (PCR) and Goldmann-Witmer Coefficient (GWC) calculation to search for evidence that Epstein-Barr virus (EBV) causes uveitis. Methods: A prospective cross-sectional study where participants with positive multiplex EBV PCR results were further investigated by: 1) real-time PCR for EBV viral loads (VL) and 2) EBV GWC. Results: Eleven of 106 consecutive uveitis patients (10.4%) had positive multiplex PCR for EBV on aqueous humor sampling and 7/11 (63.6%) were HIV-positive. Only 4/10 (40%) cases had detectable intraocular EBV VLs which were always lower than the blood or plasma VL. EBV GWC was negative in all 10 cases tested. In 9/11 (81.8%) of these cases an alternative, more plausible cause of uveitis was identified. Conclusion: We found no evidence of active intraocular replication or antibody production to prove that EBV caused uveitis in these cases. In most cases an alternative treatable cause of uveitis was identified.

Anti-infective ophthalmic preparations in general practice

Abstract Ocular infections may be bacterial, viral, fungal or parasitic in aetiology. Pharmacological preparations are available to treat infections that are caused by these groups of organisms. The majority of these preparations are intended for topical administration, although some systemically administered agents may be needed to treat or prevent specific ocular infections. This article discusses the different anti-infective options that are available to general practitioners to treat infections caused by each aetiological group. It also discusses the role that is played by povidone-iodine and antibiotic-steroid combinations to manage eye infections. A summary of all these drugs is provided in table form for easy reference.

A challenging red eye clinical quiz

Abstract The following red eye cases and this clinical quiz is not only aimed at over the counter (OTC) medication, but also illustrates the importance of referring patients who do not respond to OTC medicines or primary medical attention. The case studies are discussed in more detail after the initial case presentations. Read the case studies and decide whether the causes are bacterial, viral, or allergic and decide what treatment you would have prescribed for the patient, or if you would refer the patient.

Authors reply to Letter to the Editor– In Response to: “Smit D, Meyer D, Maritz J, et al. Polymerase Chain Reaction and Goldmann-Witmer Coefficient to Examine the Role of Epstein-Barr Virus in Uveitis”

Division of Ophthalmology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa, Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University and the National Health Laboratory Service, Cape Town, South Africa, and Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands

Polymerase Chain Reaction and Goldmann-Witmer Coefficient Testing in the Diagnosis of Infectious Uveitis in HIV-positive and HIV-negative Patients in South Africa

ABSTRACT 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.

Patterns of Uveitis at Two University-Based Referral Centres in Cape Town, South Africa

ABSTRACT Purpose: To analyze the pattern of uveitis at two tertiary hospitals in South Africa which has a high prevalence of HIV, TB and syphilis. Methods: Data of 198 patients were obtained retrospectively between August 2014 and August 2016, including patient demographics, clinical examination, special investigations and final diagnosis. Results: Infectious uveitis was the most common aetiological category (47%), followed by idiopathic (34.8%) and non-infectious (18.2%). Syphilis was the most common identifiable cause (16.2%). Other important causes were toxoplasmosis, herpes viruses, tuberculosis and HLA-B27. HIV positive patients, who constituted 40% of the study population, were more likely to present with a posterior or panuveitis (relative risk 1.50, 95% CI 1.19–1.89) and more likely to have an infectious cause compared to HIV negative patients (relative risk 2.47, 95% CI 1.82–3.35). Conclusions: This study emphasizes the importance of HIV testing and investigations for infectious causes of uveitis, especially syphilis, in this population.

Ocular and Cerebrospinal Fluid Penetration of Antiretroviral Agents

PURPOSE The ocular penetration of systemically administered antiretroviral drugs (ARVs), which is important in the clinical setting of HIV uveitis, is unknown. This study aimed to assess the ocular penetration of different antiretroviral drugs in an animal model. METHODS Twenty-five male New Zealand white rabbits were assigned to one of five treatment groups. Each group received a single oral dose of an antiretroviral drug (lamivudine, tenofovir, efavirenz, lopinavir, and raltegravir). These 5 drugs represent 4 different ARV drug classes [nucleoside reverse transcriptase inhibitors (NRTI), non-NRTI, protease inhibitors, and integrase inhibitors]. Serum, cerebrospinal fluid (CSF), and aqueous and vitreous humor samples were collected at the time of theoretical maximum serum concentration of each respective drug, for example, lamivudine 1 h, tenofovir 1 h, efavirenz 5 h, lopinavir 4 h, and raltegravir 3 h. The drug concentration in each sample was determined by means of high-performance liquid chromatography and mass spectrometry. RESULTS After a single oral dose, measurable levels of all five ARVs administered could be detected in all 4 body compartments. The limit of detection based on a signal-to-noise ratio of 1:3 for the antiretroviral agents was as follows: 1 part per billion (ppb) for lamivudine, tenofovir, and efavirenz and 0.1 ppb for lopinavir and raltegravir. The IC50 (inhibitory concentration where 50% of viral replication is inhibited by a drug) was reached for all drugs in the serum and CSF. In the aqueous humor, lopinavir failed to reach IC50 and in the vitreous humor, only efavirenz and lopinavir attained IC50 levels. CONCLUSION After a single oral dose, measurable levels of all 4 classes of ARVs could be detected in all 4 body compartments sampled. In the eye, IC50 levels were lower in the vitreous humor than in aqueous humor. IC50 levels in the serum were higher than in the CSF.