Utility of pan-bacterial and pan-fungal PCR in endophthalmitis: case report and review of the literature

Abstract

Background: Endophthalmitis is a clinical diagnosis but identification of the disease-causing agent or agents allows for a more tailored treatment. This is routinely done through intraocular fluid cultures and staining. However, culture-negative endophthalmitis is a relatively common occurrence, and a causative organism cannot be identified. Thus, further diagnostic testing, such as pan-bacterial and pan-fungal polymerase chain reactions (PCRs), may be required. BODY: There are now newer, other testing modalities, specifically pan-bacterial and pan-fungal PCRs, that may allow ophthalmologists to isolate a causative agent when quantitative PCRs and cultures remain negative. We present a case report in which pan-fungal PCR was the only test, amongst quantitative PCRs, cultures, and biopsies, that was able to identify a pathogen in endophthalmitis. Pan-PCR has unique advantages over quantitative PCR in that it does not have a propensity for false-positive results due to contamination. Conversely, pan-PCR has drawbacks, including its inability to detect viruses and parasites and its increased turnaround time and cost. Based on two large retrospective studies, pan-PCR was determined not to be recommended in routine cases of systemic infection as it does not typically add value to the diagnostic workup and does not change the treatment course in most cases. However, in cases like the one presented, pan-bacterial and pan-fungal PCRs may be considered if empiric treatment fails or if the infective organism cannot be isolated. If pan-PCR remains negative or endophthalmitis continues to persist, an even newer form of testing, next-generation sequencing, may aid in the diagnostic workup of culture-negative endophthalmitis.

Conclusion: Pan-bacterial and pan-fungal PCR testing is a relatively new diagnostic tool with unique advantages and drawbacks compared to traditional culturing and PCR methods. Similar to the tests' use in non-ophthalmic systemic infections, pan-bacterial and pan-fungal PCRs are unlikely to become the initial diagnosis test and completely replace culture methods. However, they can provide useful diagnostic information if an infectious agent is unable to be identified with traditional methods or if empiric treatment of endophthalmitis continues to fail.

Keywords: Chorioretinitis; Endophthalmitis; Intraocular infection; Next-generation sequencing; Quantitative PCR; pan-PCR.

Fig. 1

Widefield pseudocolor imaging (A) and fundus autofluorescence (B) of the right eye show subretinal infiltrates along the inferior arcade and inferior periphery. OCT B-scan through the lesion demonstrates sub-RPE infiltrates along the inferior arcade (C). Widefield pseudocolor imaging (D) and fundus autofluorescence (E) of the left eye show submacular infiltrates, with another patch in the nasal mid periphery. OCT B-scan through the macula arcade highlights sub-RPE infiltrates (F)

Fig. 2

Widefield pseudocolor imaging (A) and fundus autofluorescence (B) of the right eye at the time of lesion enlargement and widefield pseudocolor imaging (C) and fundus autofluorescence (D) following treatment. Widefield pseudocolor imaging (E) and fundus autofluorescence (F) of the left eye at the time of lesion enlargement and widefield pseudocolor imaging (G) and fundus autofluorescence (H) following treatment. The lesions in both eyes show signs of regression with overlying RPE and retinal scarring after treatment

Fig. 3

Illustration comparing real-time PCR, pan-PCR, and next-generation sequencing based on the item being measured, cost, turnaround time, sensitivity, and specificity. The graphic also denotes unique drawbacks in each of the methods