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that there is even among ophthalmic nurses working at the ophthalmology outpatient department of hospitals an extensive lack of knowledge about viral HSV-1 keratitis [Schaftenaar E; unpublished data]. For example, when we retrospectively reviewed patient files of patients diagnosed with keratitis, topical antivirals were prescribed ex- clusively to patients presenting with cutaneous HZO [Schaftenaar E; unpublished data]. In our study, we demonstrated that polymerase chain reaction (PCR) analysis of cor- neal swabs is a valuable diagnostic platform to detect viral DNA and supports clinical observations of herpetic keratitis in cases with epithelial inflammation (chapter 3) [46]. We consider PCR analysis of corneal swabs of significant diagnostic value and propose that this methodology should be introduced in the routine management of patients in rural South Africa presenting with epithelial keratitis of potential viral aetiology. How- ever, in cases with subepithelial inflammation, PCR results of corneal swabs were often negative, even though the clinical presentation and response to antiviral treatment was suggestive for herpetic keratitis (chapter 3) [46]. Consequently, determination of the pathogen involved using PCR analysis of corneal swabs in keratitis patients remains challenging. As ophthalmological expertise in these settings is very limited, correct diagnosis solely based on clinical characteristics is highly unlikely. Corneal scraping might be an alternative to corneal swabbing in cases with subepithelial inflammation and will improve aetiological diagnosis [53]. However, corneal scraping bears higher risks (e.g. bacterial superinfection) as the procedure is more invasive than corneal swab- bing. Future studies to elucidate the diagnostic value and potential complications of corneal scraping in high HIV prevalent settings with limited ophthalmological expertise is warranted. In our study, bacteria were detected in almost half of the viral keratitis cases, but unlike other studies bacterial superinfection of the cornea was not associ- ated with poorer visual outcome (chapter 3) [46, 54]. However, we do advocate to perform microbial examination of corneal swabs because bacterial superinfections are common and might lead to poorer outcomes if left untreated. Fortunately, microbial analysis, including Gram-stain microscopy and culture, of corneal swabs for bacteria and fungi is available in most hospitals in South Africa. However, to be cost-effective in resource-limited settings, we consider that laboratory analyses of corneal swabs (PCR analysis and microbial examination) should be performed at District level hospitals only. A fungus was detected in only one keratitis case, which is in contrast to a study from Tanzania that reports fungi as a common causative pathogen among culture positive cases of microbial keratitis [55]. The low number of fungal keratitis cases observed in our study may be due to the exclusion of traumatic keratitis as most fungal keratitis cases are trauma related [56]. Furthermore, this may also be correlated to geographical differ- ences as fungal keratitis is more likely to occur toward tropical latitudes [44, 56]. Anterior uveitis was an important complication of infectious keratitis and was significantly more common among HIV-infected than HIV-uninfected individuals (chapter 3) [46]. Thus,

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concomitant anterior uveitis in patients presenting with infectious keratitis may point at undiagnosed HIV infection, which warrants subsequent HIV counselling and testing.

Early diagnosis of infectious keratitis and consequently initiation of targeted antimicro- bial treatment is of paramount importance to prevent ocular morbidity because poorer visual outcome was associated with increased time between onset of symptoms and first presentation at the ophthalmology department of hospitals (chapter 3) [46]. This remains challenging, especially in resource- and skills-constrained settings (chapter 3) [44, 46, 56]. Current management of infectious keratitis in rural South Africa emphasizes (presumptive) antibacterial treatment rather than identifying the triggering pathogen [57]. In addition, topical antivirals (e.g. acyclovir) are unavailable at PHC facilities and were hardly used in the ophthalmology outpatient department of hospitals before the study [Schaftenaar E; unpublished data]. Our results suggest that current manage- ment leads to significant under-treatment and possible preventable blindness as viral aetiology is very common (chapter 3) [46]. Therefore, we advocate that presumptive treatment of patients presenting with infectious keratitis to PHC facilities should include both topical antibiotic and antiviral treatment to prevent ocular morbidity. To improve diagnosis, microbial examination and PCR analysis, in cases with epithelial inflammation, of corneal swabs should be performed in patients presenting with infectious keratitis. In addition, training of PHC nurses on basic ophthalmology skills including eye exami- nation is warranted to ensure early identification of keratitis, initiation of appropriate treatment and reinforce prompt referral to ophthalmology outpatient departments of hospitals to prevent further delay.

HErPES ZOStEr OPHtHAlmIcuS

HZO is the clinical manifestation of reactivation of latent VZV infection in the ophthalmic branch of the trigeminal ganglion [58]. Ocular involvement occurs in more than half of patients with untreated cutaneous HZO, leading to ocular morbidity [49-50, 59-60]. Rela- tive mild acute ocular complications of HZO may progress to chronic disease, which are associated with severe visual impairment if left untreated [49-50]. HIV-infected individu- als are at increased risk of developing HZO, but limited data are available on the ocular manifestations of HZO in high HIV prevalence settings in sub-Saharan Africa [45, 51, 61].

In our study on HZO, ocular complications were classified as “early” or “late” based on stage of disease progression and (potential) restoration of normal vision, which resulted in a unique clinical classification system of ocular complications of HZO (chapter 4) [62]. Our study revealed that the spectrum of ocular complications of HZO among patients presenting to the ophthalmology outpatient department in a high HIV prevalence setting is diverse and that late-stage ocular complications are common and associated

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