Ring infiltrate revisited: A diagnostic masquerade unmasking Pythium insidiosum keratitis

Dear Editor,

We read with great interest the recent article on ring infiltrates (RIs) in Pythium keratitis.[1] The authors have elegantly highlighted a clinically significant yet under-recognized presentation that frequently leads to diagnostic ambiguity. We sincerely congratulate the authors for bringing attention to this important masquerade and wish to share our own clinical experience, which further substantiates this diagnostic challenge. RI is traditionally considered a hallmark of fungal or Acanthamoeba keratitis. However, in clinical practice, it may also be encountered in bacterial and, less commonly, viral keratitis, thereby compounding the diagnostic dilemma.[2] As emphasized in the published case series, RI may also be a presenting or evolving feature of Pythium keratitis, often resulting in misdiagnosis and delay in appropriate therapy. In our clinical practice, we encountered five patients with RI, all of whom were ultimately diagnosed with Pythium insidiosum keratitis following microbiological confirmation.

In our case series, Case 1 was a 45-year-old male with vegetative trauma presenting after 12 days with hand movements (HM) vision and a central infiltrate with well-defined RI at presentation; he was initially treated as fungal keratitis but failed to respond and subsequently underwent therapeutic penetrating keratoplasty (TPK). Case 2 was a 52-year-old female without trauma presenting at 10 days with HM vision, peripheral RI with hypopyon; she was initially treated as bacterial keratitis with fortified antibiotics, but was later confirmed to have Pythium, resulting in corneal scarring. Case 3 involved a 38-year-old male with trauma presenting at 8 days with HM vision and early RI formation; initially presumed fungal keratitis, rapid progression necessitated TPK despite delayed antipythium therapy. Case 4 was a 60-year-old female presenting after 14 days with perception of light (PL) vision; RI developed during the disease course and was initially suspected to be viral keratitis due to atypical presentation, but was later confirmed as Pythium and healed with a dense corneal scar. Case 5 was a 50-year-old male with trauma presenting after 7 days with PL with projection of rays vision, central infiltrate with surrounding RI and impending perforation; initial antifungal therapy failed, and delayed diagnosis led to emergency TPK [Figure 1a-e and Table 1].

Figure 1.

Diffuse slit lamp images depicting spectrum of ring infiltrates in Pythium insidiosum keratitis (a) 6 mm × 6 mm central dense stromal infiltrate with a well-defined circumferential ring infiltrate along with central thinning (b) 4 mm × 4 mm classic annular full-thickness ring-shaped stromal infiltrate, surrounding corneal edema and central perforation. (c) 4 mm × 4 mm central full-thickness ring infiltrate associated with hypopyon. (d) Advanced disease with ring infiltrate, central necrosis, and features suggestive of impending perforation. (e) Peripheral/paracentral ring infiltrate with surrounding stromal haze abutting the nasal limbus

Table 1.

The clinical and microbiological characteristics of these cases are summarized below

Case	Age/Sex	Eye	Trauma	VA at presentation	Duration (days)	RI (timing)	Initial diagnosis	Smear	Culture	Treatment	Outcome
1	45/Male	LE	Yes	HM	12	Presentation	Fungal	No organism	Zoospore +	Antifungal → APT → TPK	Failed graft
2	52/Female	RE	No	HM	10	Presentation	Bacterial	No organism	Zoospore +	Fortified antibiotics → APT	Scar
3	38/Male	RE	Yes	HM	8	Early	Fungal	Aseptate filaments	Zoospore +	Antifungal → APT → TPK	Failed graft
4	60/Female	LE	No	PL	14	Delayed	Viral	No organism	Zoospore +	Antiviral → APT	Scar
5	50/Male	LE	Yes	PLPR	7	Presentation	Fungal	Aseptate filaments	Zoospore +	Antifungal → APT → TPK	Perforation

VA: Visual acuity, RI: Ring infiltrate, APT: Antipythium therapy, TPK: Therapeutic penetrating keratoplasty, HM: Hand movements, PL: Perception of light, PLPR: Perception of light with projection of rays, LE: Left eye, RE: Right eye

These cases reinforce a crucial clinical insight: RI represents a diagnostic dilemma rather than a disease-specific sign. The overlap with fungal, bacterial, viral, and Acanthamoeba keratitis frequently leads to inappropriate initial therapy. Similar to the observations reported by the authors, delayed initiation of antipythium therapy in our cases resulted in disease progression, corneal melt, and need for surgical intervention. The inability to differentiate Pythium from fungal filaments on routine smear examination further compounds the challenge, making culture-based confirmation, particularly demonstration of zoospore formation is essential.[3] Early suspicion, prompt microbiological correlation, and timely initiation of targeted therapy (e.g., linezolid and azithromycin) can significantly alter outcomes.[4] We emphasize that clinicians should maintain a high index of suspicion for Pythium keratitis in any atypical RI, especially in cases with rapid progression, poor response to antifungal or antibiotic therapy, or presence of characteristic features such as tentacular extensions and stromal guttering.[5] In conclusion, we echo the author’s important message that RI should not be considered pathognomonic of any single etiology. Instead, it should alert the clinician to the possibility of Pythium, particularly in endemic regions. Strengthening microbiological support and enhancing clinical awareness are key to improving diagnosis and outcomes in such challenging cases. We once again congratulate the authors for their insightful contribution and thank them for highlighting this important clinical entity.

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.