Abstract
This study highlights the clinical presentation of ring infiltrates (RI) in Pythium keratitis, typically associated with fungal or Acanthamoeba keratitis, emphasizing diagnostic and therapeutic challenges. We present a retrospective case series of seven patients diagnosed with Pythium keratitis who developed RI, either at presentation or during the disease course. Diagnosis was confirmed by microbiological examination, and all patients received antipythium therapy within 1 week of presentation. Among the seven patients, all exhibited RI, leading to diagnostic confusion due to its common association with fungal and Acanthamoeba keratitis. Prompt microbiological confirmation enabled targeted therapy, but initial presentation caused diagnostic challenges, especially in settings without routine microbiological support. RI is not uncommon in Pythium keratitis and can result in misdiagnosis as fungal keratitis, particularly in resource-limited settings. Recognizing RI as a feature of Pythium keratitis and ensuring early microbiological confirmation can enhance diagnostic accuracy and improve patient outcomes.
Keywords: Antipythium therapy, Pthium keratitis, ring infiltrate, therapeutic keratoplasty
Introduction
Pythium insidiosum is a filamentous oomycete morphologically similar to fungi, but it lacks ergosterol in its cytoplasmic membrane, resulting in a poor response to antifungal drugs.[1] Medical management involves topical oxazolidinone (linezolid) and topical/systemic macrolides (azithromycin).[2] Even with appropriate medical management, most cases of Pythium keratitis are fulminant and require therapeutic penetrating keratoplasty (TPK).[3]
Clinically, it presents as yellowish-white infiltrates with feathery margins, tentacle-like projections into the surrounding healthy cornea, subepithelial pinhead-shaped infiltrates away from the margins, and guttering around the infiltrates.[3,4] Ring infiltrate (RI), which is corneal infiltration in a ring-like manner away from the area of central infiltrate, has also been observed in a few cases of Pythium keratitis, but rarely.[4,5] We report a case series of seven patients with Pythium keratitis who presented with or developed RI.
Case Series
Of the seven patients, five were males (71.4%). Two patients (28.6%) had a history of trauma with vegetative matter. The mean age of the patients was 49 ± 15.59 years. The mean duration of symptoms was 11.71 ± 3.84 days. Visual acuity (VA) was determined as less than counting fingers at 1 meter in all cases. All patients had pinhead infiltrates, tentacle-like projections, and subsequent guttering. Of the seven patients with RI, five had RI on presentation [71.43%, Cases 1–5, Figure 1a-e]. Cases 6 [Figure 1f] and 7 [Figure 1g] developed signs on the 4th and 11th days of presentation, respectively. The average time of occurrence of RI from the 1st day of symptoms was 13.28 ± 4.89 days. Microbiological examinations were performed on the same day for all the patients. Three patients showed the presence of aseptate, broad filaments in Gram’s stain as well as 1% potassium hydroxide stain. All patients demonstrated zoospore formation on culture within a week, which was considered confirmatory. The details of the patients and microbiological results are presented in Tables 1 and 2.
Figure 1.
Slit lamp picture of all patients having ring infiltrate (a-e) At presentation (f) At 4th day, and (g) At 7thday
Table 1.
Demographical and clinical data of patients
| Age, sex, eye | Trauma | VA on 1st visit | Duration of symptoms (days) | Appearance of ring infiltrate | Duration between start of APT and presentation (days) | Interval between presentation and TPK (days) | Follow-up (months) | Outcome | ||
|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
|||||||||
| From symptoms | From presentation | VA | Anatomical | |||||||
| 31, male, left eye | No | HM | 15 | 15 | SD | 5 | 18 | 24 | PLPR | Failed graft |
| 63, male, right eye | No | HM | 15 | 15 | SD | 6 | 23 | 17 | PLPR | Failed graft |
| 43, male, right eye | No | HM | 8 | 8 | SD | 6 | 8 | 26 | CFCF | Failed graft |
| 58, female, left eye | No | HM | 15 | 15 | SD | 7 | 13 | 5 | HM | Graft clear, cataract |
| 23, male, left eye | No | PLPR | 6 | 6 | SD | SD | NA | 3 | CFCF | Corneal scar |
| 59, female, left eye | Yes | HM | 8 | 12 | 4 | SD | NA | 5 | CFCF | Corneal scar |
| 66, male, right eye | Yes | PLPR | 15 | 22 | 7 | SD | NA | 5 | HM | Corneal scar |
APT: Antipythium treatment, CFCF: Counting fingers close to face, HM: Hand movements, NA: Not applicable, PL: Perception of light, PR: Projection of rays, SD: Same day, TPK: Therapeutic penetrating keratoplasty, VA: Visual acuity
Table 2.
Microbiological characteristics of patients
| Case | Smear report | Culture report: Corneal scraping | Culture report: Half corneal button |
|---|---|---|---|
| 1 | No organism | Zoospore formation | Zoospore formation |
| 2 | No organism | Zoospore formation | Zoospore formation |
| 3 | No organism | Zoospore formation | Zoospore formation |
| 4 | No organism | Zoospore formation | Zoospore formation |
| 5 | Broad, aseptate, folded, fungal-like filaments | Zoospore formation | Zoospore formation |
| 6 | Broad, aseptate, folded, fungal-like filaments | Zoospore formation | Zoospore formation |
| 7 | Broad, aseptate, folded, fungal-like filaments | Zoospore formation | Zoospore formation |
Antipythium therapy (APT) in our cases consisted of topical Linezolid (2%, hourly, until resolution of infection), topical azithromycin ointment (1%, twice daily, until resolution of infection), and systemic azithromycin (500 mg, twice daily for 2 weeks). Three patients (Cases 5, 6, 7) were started on APT on the day of presentation, as they showed the presence of aseptate, broad filaments on smear evaluation. For the other four cases, APT was started within a week. The average time between presentation and the start of APT was 3.42 ± 3.01 days. Four patients, in whom APT was started late, required TPK due to corneal melting. The average time interval between presentation and TPK was 15.50 ± 5.59 days. The remaining three cases could be managed medically only.
Out of these four patients, three experienced graft failure within 3 months, and one patient retained a clear graft but had reduced final VA due to the development of cataract. The remaining three patients developed leukomatous corneal scar and will require secondary intervention.
Discussion
Pythium keratitis is difficult to manage because of its morphological and clinical resemblance to fungi, relatively low incidence, aggressive nature, and resistance to antifungal drugs.[2,6] Typical clinical features such as reticular-dot infiltrates, tentacle-like extensions, and guttering help raise clinical suspicion.[3,4] RI has been extensively described in Acanthamoeba and fungal keratitis and rarely in Pythium keratitis.[5,7,8] In their study, Bagga et al. reported the incidence of RI to be approximately 2%.[2] However, a rabbit model study by Kalra et al. observed RI as the most consistent finding on initial presentation.[9] Similarly, we report seven cases of culture-proven Pythium keratitis with RI. Most patients presented to us within 2 weeks of symptom onset. Since Pythium filaments cannot be differentiated from fungal filaments on routine smear examination, zoospore formation on culture was considered confirmatory. After a standard microbiological examination, appropriate management was instituted.
Despite medical management, four cases worsened and required TPK. It was noted that all patients who were started on APT on the same day of presentation could be managed medically. The rest required TPK, highlighting the crucial role of timely diagnosis of Pythium keratitis. Here, the role of the ophthalmologist in having clinical suspicion becomes important. Once clinical suspicion is raised, it can be shared with the microbiologist to aid in the detection and confirmation of Pythium keratitis. It should be noted that for four out of five cases presenting with RI, the presumptive diagnosis of Pythium was not initially made. In addition, negative smears led to patients being treated for fungal keratitis. It was only when zoospore formation was seen that APT could be started. Unfortunately, by then, it was too late, and the corneas had already begun showing collagenolysis, leading to the need for TPK.
Therefore, we conclude that RI is an important clinical sign of Pythium keratitis. If it is present along with other common clinical signs of Pythium keratitis, it should help in narrowing the presumptive diagnosis. Such a presumptive diagnosis should then be shared with microbiologists. In addition, if one encounters an unusual case of RI that is not responding to antifungals, Pythium keratitis must be considered a close differential.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
This study was funded by Hyderabad Eye Research Foundation, Hyderabad, India.
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