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Dr. Min-Chien Hsiao · Ophthalmology Notes
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📑 RCT secondary analysis · Jacobs et al. 2026 · Am J Ophthalmol · ZEDS Trial Research Group
Latest Research · Keratitis · HZO

Recurrent Stromal Keratitis After HZO
Some recurrent cases had recently stopped steroid drops

A May 2026 secondary analysis of the Zoster Eye Disease Study (ZEDS) in American Journal of Ophthalmology (Jacobs et al.). ZEDS was a US/Canada/NZ 95-center, 527-patient double-masked RCT comparing valacyclovir 1000 mg/day × 1 year vs placebo. Key findings: 105/527 (20%) developed recurrent, new or worsening stromal keratitis; 75% were found at scheduled visits (rather than at unscheduled visits for new complaints); 67% had SK at or before enrollment; 18 of 48 people off topical steroid at SK (38%) had stopped within the prior 3 months; this is not the risk among all who stopped; at SK onset, 90% of the 52 on topical steroids (47) were dosing ≤ once daily, and these 47 were evenly split between high- and low-potency; 88% of low-potency users were treated with an increase in frequency only, without switching to high-potency; 11/105 had oral valacyclovir newly added at event management; this does not describe baseline oral use or mean all HZO patients can omit antivirals; vision essentially preserved (Snellen 20/25 → 20/27). Cross-referenced with the Taiwan NHI drug reimbursement rules (updated 2026-10-22), section 10.7.1.1 (systemic anti-herpetic agents restricted to listed conditions, course capped at 10 days in principle) and section 14.2 (ophthalmic acyclovir restricted to any one of: V1 involvement threatening the cornea, herpetic keratitis or corneal ulcer, or acute retinal necrosis). ZEDS's 1-year suppression protocol is not within Taiwan NHI's listed conditions.

20 min readLast updated · 2026-11-05Dr. Hsiao →
Decisions about starting, stopping, tapering, or chronically maintaining any medication — particularly topical steroids and oral antivirals — should be made by your physician based on your individual case. Taiwan NHI references follow the NHI drug reimbursement rules (updated 22 October 2026, ROC 115-10-22). Those rules do not list the Shingrix vaccine and set no specific conditions for individual topical-steroid products; this article does not speculate on their coverage or cost — please consult your pharmacist or the NHIA portal for those.
In this article· 11 sectionsClick to collapse
  1. 11. Common clinic scenarios
  2. 22. Common patient Q&As
  3. 33. Key takeaways: 8 things you really need to know
  4. 44. Background: why does shingles "hit the eye"?
  5. 55. What is ZEDS, and why does this dataset matter?
  6. 66. The 6 clinical lessons from ZEDS
  7. 77. Topical steroid tiers (ZEDS definitions)
  8. 88. Taiwan NHI antiviral coverage conditions
  9. 99. When to see your doctor immediately
  10. 1010. Conclusion: HZO is not a 7-day disease — it's a 7-year disease
  11. 11References
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帶狀疱疹眼疾後反覆角膜炎：從皮疹到追蹤的敘事圖 HZO narrative with V1 rash and stromal inflammation. In the ZEDS recurrence analysis, 18 of 48 people not using steroids at the event (38%) had stopped them within the preceding 3 months; this is not the recurrence rate among everyone who stopped. Treatment and tapering require individualized ophthalmic assessment. Some recurrent cases had recently stopped drops Recurrent stromal keratitis after HZO — at a glance ① Rash here = high eye-risk zone Forehead Upper lid Nose tip ★ Virus travels along trigeminal V1 into the eye ★ Hutchinson sign (nose-tip rash) = high eye risk ② Inflammation is in the "stromal" middle layer Eyeball Cornea zoom (cross-section) Epithelium Stroma ← SK inflammation Endothelium Recurrent → scar → vision loss ③ Recent cessation among recurrent cases Rash onset Day 0 Acute Rx Oral antiviral 7–10 d + topical steroid Maintenance Low-potency drop gradual taper STOP Stopped in prior 3 mo 18/48 cases (38%) Follow-up continue follow-up 3M Visit every 3 mo 75% found at check-ups not extra symptom visits found by slit-lamp exam ↓ Low-potency maintenance 88% stayed low-potency treated by dosing more often may lessen IOP rise / cataract risk Don't abruptly stop Recent cessation 18/48 cases (38%) Individualized tapering Source: ZEDS trial (Jacobs et al. 2026) · n = 527 · 18-month follow-up
Recurrent stromal keratitis after HZO: inflammation in the corneal stroma can repeatedly affect vision. In the ZEDS recurrence analysis, 18 of 48 people not using steroids at the event (38%) had stopped them within the preceding 3 months; this is not the recurrence rate among everyone who stopped. Oral antivirals were newly added at event management in 11/105. This does not mean the others were not already taking them or that all HZO patients can omit antivirals. Treatment and tapering require individualized ophthalmic assessment. Source: Jacobs et al. 2026, ZEDS SK secondary analysis.

1. Common clinic scenarios

'Doctor, five years ago I had a shingles rash on my forehead, scalp and upper eyelid, and my cornea got inflamed too. Ophthalmology gave me steroid eye drops, tapered me down, and eventually I stopped. About two or three months after stopping, this eye is getting red and a bit hazy again — is it back?'

'Doctor, I was hospitalized 10 years ago for herpes zoster ophthalmicus. Ophthalmology said to come back regularly, but I felt fine for years so I stopped going. At a recent routine check, ophthalmology found deep inflammation in my cornea — I felt absolutely nothing. Is that serious?'

'Doctor, I recently saw dermatology for shingles and finished a 7-day course of oral antiviral. The skin healed but my eye is still occasionally light-sensitive and slightly sore. Do I need to keep taking the oral antiviral? For how long?'

All three scenarios revolve around the same point: the eye component of herpes zoster ophthalmicus (HZO) is usually not "a 7-day oral antiviral course and you're done" — it tends to be a relapsing, chronic process. A May 2026 secondary analysis of the Zoster Eye Disease Study (ZEDS) SK end point by Jacobs et al. in American Journal of Ophthalmology gives us six concrete clinical lessons. This article distils them in clinic-friendly language and cross-references the relevant Taiwan NHI.

2. Common patient Q&As

Q1: What is HZO? Is it the same as stromal keratitis (SK)?
A: Not the same — it's a parent-child relationship. Herpes zoster ophthalmicus (HZO) is the umbrella term for any eye involvement when varicella-zoster virus (VZV) reactivates along the first branch (V1) of the trigeminal nerve — forehead, upper eyelid, tip of nose. HZO manifestations include: stromal keratitis (SK), dendritiform epithelial keratitis (DEK), endothelial keratitis (EK), iritis (IR), plus neuralgia, conjunctivitis, optic neuritis, acute retinal necrosis, etc. SK is the most common complication — in ZEDS, 105 of the 160 participants (66%) with a primary end point within 12 months had SK. SK means inflammation in the middle ("stromal") layer of the cornea; it can cause corneal opacification, neovascularisation, and permanent scarring — a major cause of vision loss after HZO.
Q2: How long after the initial HZO episode can it recur?
A: It can recur 5, 10, even decades later. Ocular complications of HZO are by nature chronic, relapsing. Tran et al. 2016 in Ophthalmology showed the 5-year recurrence rate of HZO eye disease or rash is about 25%. The main ZEDS trial (Cohen et al. 2025 JAMA Ophthalmol) confirms that patients with any prior SK/DEK/EK/IR complication carry a substantial 1-year recurrence rate. The Jacobs et al. 2026 secondary analysis further showed 70 of the 105 people with recurrent SK (67%) had SK before or at enrollment; the virus can shed asymptomatically and maintain low-level immune activation for years. HZO should not be treated as "over once acute treatment is done" — it is a chronic relapsing disease.
Q3: Why every 3 months if I have no symptoms?
A: Because ZEDS showed 75% of SK was found at scheduled visits (rather than at unscheduled visits for new complaints). In the Jacobs et al. 2026 data, 79 of 105 SK events (75%) were diagnosed at scheduled routine visits — not at unscheduled patient-initiated visits for redness/pain/blur. The study did not record symptoms directly, but the authors interpret this as suggesting that SK needing treatment typically emerges without symptoms. Early SK often starts as a small sectorial infiltrate (as described by Mondino 1986); the patient may not yet notice it, but if untreated it spreads centrally, scars, and brings in new vessels. Slit-lamp examination (with fluorescein and blue light) picks up changes the patient cannot feel. "No symptoms" does not mean "no inflammation" — this is the central value of scheduled surveillance.
Q4: Why does "relapse soon after stopping topical steroids" matter so much?
A: In the ZEDS recurrence analysis, 18 of 48 people not using steroids at the event (38%) had stopped them within the preceding 3 months; this is not the recurrence rate among everyone who stopped. Treatment, tapering and maintenance require individualized ophthalmic assessment.
Q5: My doctor said I can switch to a low-potency drop long-term — is that safe?
A: ZEDS data support this direction, but the individual decision rests with your physician. ZEDS classified topical steroids into two tiers: high-potency (prednisolone acetate 1%, difluprednate 0.05%, dexamethasone 0.1%, prednisolone phosphate 1%) and low-potency (loteprednol 0.2%, fluorometholone 0.1%/0.25%, prednisolone acetate 0.12%, rimexolone 1%). Among the 52 patients on a topical steroid at SK onset, 47 were dosing once daily or less; among these 47, the high/low split was nearly 1:1 (21 vs 26; p = 0.47). This p value only compares the proportions of high- and low-potency use among people who had already relapsed; it cannot show which potency better prevents relapse. The authors read this as suggesting that higher potency adds no extra protection and low potency appears sufficient, but that is an inference: the study did not compare relapse rates between the two groups. And for managing recurrence, 88% (23/26) of low-potency users were treated with an increase in dosing frequency only, without switching to high-potency. The authors conclude that low-potency topical steroids should be considered for treatment and ongoing suppression of SK. Of the 105 SK patients, none was using difluprednate when SK occurred, and only one, who had been on no topical steroid, was treated with this very high-potency drop (4×/day). Compared with high-potency steroids, low-potency steroids are generally thought to carry a possibly lower long-term risk of IOP rise and cataract progression — but that's not zero. Any patient on long-term topical steroid still needs IOP and lens monitoring.
Q6: Do I need long-term oral valacyclovir? Will NHI cover it?
A: Oral antivirals were newly added at event management in 11/105. This does not mean the others were not already taking them or that all HZO patients can omit antivirals. Treatment and tapering require individualized ophthalmic assessment.

Taiwan NHI (drug reimbursement rules, updated 2026-10-22):
• §10.7.1.1 systemic anti-herpetic agents (acyclovir, famciclovir, valaciclovir) — restricted to: herpes zoster/HSV involving V1 with potential corneal threat; herpes zoster/HSV keratitis or corneal ulcer; acute retinal necrosis; zoster/HSV in immunocompromised, cancer or transplant patients; herpes zoster within 3 days of rash on the head/neck or genital area (up to 5 days of oral or topical treatment); etc.
• Same section, point 3 states explicitly: "Except for the above specific conditions, treatment is limited to a 10-day course; oral, injectable and topical formulations must be used as a single agent, not combined."
• So ZEDS's "1-year suppression" use is not within Taiwan NHI's listed conditions; if your treating physician recommends long-term low-dose suppression on clinical grounds, it usually requires out-of-pocket payment.
• An acute HZO course of up to 10 days is covered when one of the listed conditions applies (e.g. V1 involvement threatening the cornea); this section requires no prior authorisation and does not restrict which specialty may prescribe. Discuss the details with your doctor.
Q7: What happens in the worst case if recurrent inflammation is not properly treated?
A: Corneal neovascularization, permanent scarring, vision loss. Long-term changes in poorly controlled HZO include: (1) corneal neovascularization — new vessels grow into the normally avascular cornea, causing opacification and reduced acuity; (2) corneal scarring — repeated stromal inflammation leaves permanent opaque areas; (3) loss of corneal sensation — the trigeminal nerve is damaged by the virus, causing neurotrophic keratopathy that heals poorly and ulcerates easily; (4) corneal thinning and structural instability — rarely progressing to ulceration with perforation. Corneal transplantation may eventually be needed, but the inflamed and denervated HZO cornea carries higher recurrence and rejection risk after transplant. The whole "regular surveillance + low-dose maintenance + don't abruptly stop steroid" strategy aims to keep the cornea in the reversible, scar-free, avascular state.

3. Key takeaways: 8 things you really need to know

30-second takeaways

  • HZO is chronic-relapsing: 5-yr recurrence ~25%; 67% of recurrent-SK patients had SK before or at enrollment
  • SK is the dominant complication: 66% of the 160 ZEDS participants with a primary end point within 12 months; 20% (105/527) of trial patients had recurrent/new/worsening SK
  • 75% found at scheduled visits: rather than at unscheduled visits for new complaints; scheduled 3-month follow-up is the main diagnostic route — don't wait until you "feel" something
  • In the ZEDS recurrence analysis, 18 of 48 people not using steroids at the event (38%) had stopped them within the preceding 3 months; this is not the recurrence rate among everyone who stopped.
  • Consider low-potency steroids: at relapse, high- and low-potency users were similar in number (p = 0.47), but this only compares proportions and cannot show which better prevents relapse; 88% of low-potency users were treated by increasing dosing frequency
  • Oral antivirals were newly added at event management in 11/105. This does not mean the others were not already taking them or that all HZO patients can omit antivirals. Treatment and tapering require individualized ophthalmic assessment.
  • Vision is preserved: enrollment logMAR 0.10 (20/25) → 12-month 0.13 (20/27), not statistically different
  • Taiwan NHI restricts use to listed conditions and short courses: under the NHI drug reimbursement rules (updated 2026-10-22), section 10.7.1.1 caps systemic anti-herpetic courses at 10 days in principle; 1-year suppression is not within NHI's listed conditions

4. Background: why does shingles "hit the eye"?

The pathogen is varicella-zoster virus (VZV). After childhood chickenpox, VZV is not cleared from the body but stays latent in sensory ganglia (dorsal root and trigeminal). Aging, immune decline, stress, illness, chemotherapy etc. can reactivate VZV along a single ganglion, producing a rash along that dermatome — this is shingles (zoster).

When reactivation occurs in the first division of the trigeminal nerve (the ophthalmic nerve, V1), the rash appears on the forehead, upper eyelid, tip and side of the nose — this is herpes zoster ophthalmicus (HZO). Because V1 supplies sensation to the cornea, conjunctiva, eyelids and tip of the nose, VZV can travel along the nerve to involve the eye itself; the retina has no V1 sensory supply, but it is occasionally affected through mechanisms such as vasculitis (e.g. acute retinal necrosis). A key clinical clue is Hutchinson's sign — rash extending to the tip of the nose indicates involvement of the nasociliary branch of V1 and a much higher risk of eye involvement.

Old vs current view: historically, HZO ocular complications were considered "purely inflammatory, no remaining virus," so steroids were the only treatment. Three decades of evidence (Wilson 1992, Cohrs 2008, Pavan-Langston 1995, Hu 2010, Li 2018 etc.) show that VZV can shed asymptomatically and maintain low-grade immune activation for years; recurrent SK has both an infectious and an inflammatory component. This shift in understanding underpinned the design of the ZEDS trial — if infection contributes, then long-term oral antiviral suppression ought to reduce recurrence.

5. What is ZEDS, and why does this dataset matter?

The Zoster Eye Disease Study (ZEDS) is the largest, most rigorously designed RCT for recurrent HZO eye disease (ClinicalTrials.gov: NCT03134196). Basic design:

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ItemDetail
Participants527 patients with prior HZO; stratified by age (< 60 / ≥ 60) and disease phase (recent / chronic)
AllocationDouble-masked randomization: valacyclovir 1000 mg/day × 1 year vs placebo
Follow-up18 months, with scheduled ophthalmology visits every 3 months (slit-lamp, visual acuity, IOP, etc.)
Primary end pointsRecurrent, new or worsening stromal keratitis (SK), SK with ulceration (SKU), endothelial keratitis (EK), iritis (IR), dendritiform epithelial keratitis (DEK)
Scale95 sites (US 85 + Canada 9 + NZ 1), Nov 2017 – Jun 2024
Main result (Cohen 2025, JAMA Ophthalmology)1-year valacyclovir suppression reduced SK/DEK/IR/EK recurrence at 18 months; 12-month primary endpoint not statistically significant, 18-month secondary endpoint significant

Jacobs et al. 2026 is the "SK secondary analysis" of ZEDS — unpacking the 105 SK relapse cases: who, when, on what medication, how was the relapse managed, and what was the visual outcome. This is a prespecified secondary analysis of randomized-trial data, reviewed retrospectively (relapse treatment was at the investigators' discretion) and one of the most complete datasets on SK management after HZO.

6. The 6 clinical lessons from ZEDS

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LessonZEDS dataClinical implication
1. SK is usually found at scheduled visits 79/105 (75%) diagnosed at scheduled visits HZO patients can't wait until symptoms appear; 3-monthly follow-up is the baseline
2. New oral prescriptions do not describe baseline treatment Oral antivirals were newly added at event management in 11/105. This does not mean the others were not already taking them or that all HZO patients can omit antivirals. Treatment and tapering require individualized ophthalmic assessment. Treatment and tapering require individualized ophthalmic assessment.
3. Consider low-potency steroids Among relapsed patients, high vs low potency use nearly 1:1 (p = 0.47); 88% of low-potency users were treated by increasing frequency Long-term low-potency maintenance, possibly lower IOP rise and cataract progression risk
4. Don't abruptly stop steroid In the ZEDS recurrence analysis, 18 of 48 people not using steroids at the event (38%) had stopped them within the preceding 3 months; this is not the recurrence rate among everyone who stopped. Stopping, tapering and maintenance require individualized ophthalmic assessment; a proportion among recurrent cases does not estimate individual risk after stopping.
5. p = 0.47 does not compare prevention This p value only compares the proportions of high- and low-potency use among people who had already relapsed; it cannot show which better prevents relapse This study cannot show that long-term high-potency use prevents relapse better, while its side-effect risk is generally thought to be possibly higher; the authors suggest considering low-potency for treatment and ongoing suppression
6. Vision can be preserved Enrollment logMAR 0.10 (20/25) → 12-mo 0.13 (20/27), not statistically different Active surveillance + early low-dose intervention preserves vision in most cases

7. Topical steroid tiers (ZEDS definitions)

ZEDS applied the following tiers (the Jacobs 2026 paper says per the trial protocol; clinically difluprednate is generally regarded as twice as potent as prednisolone acetate 1%, but ZEDS grouped it with other high-potency agents):

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PotencyAgents listed by ZEDS
High-potency prednisolone acetate 1%, difluprednate 0.05%, dexamethasone 0.1%, prednisolone phosphate 1%
Low-potency loteprednol 0.2%, fluorometholone 0.1%/0.25%, prednisolone acetate 0.12%, rimexolone 1%

* Note: the ZEDS protocol (version 3.0, March 2020, posted on ClinicalTrials.gov) recommends prednisolone acetate 1% or loteprednol 0.5% for participants who need topical steroids, at the investigator's discretion. Jacobs 2026's potency list includes only loteprednol 0.2% (low potency) and does not say where 0.5% falls.

About Taiwan prescribing: whether each agent is available, NHI-covered, or its self-pay cost in Taiwan — please consult your prescribing physician, pharmacist, or the latest NHIA announcements. This article does not make brand-specific coverage claims. The point here is the "potency-tier concept," not a brand recommendation.

8. Taiwan NHI antiviral coverage conditions

The following summary covers the wording of the antiviral conditions in the Taiwan NHI drug reimbursement rules (updated 22 October 2026, ROC 115-10-22). Items or scenarios the rules do not explicitly address are not commented on here (e.g. individual topical steroid brands; the Shingrix vaccine is not listed in those rules). For actual coverage, duration, and applicability, refer to your prescriber, pharmacist, or the latest NHIA announcements.

✅ §10.7.1.1 Systemic anti-herpetic agents (oral / IV acyclovir, famciclovir, valaciclovir)

Main coverage conditions (not the full rule text; all eye-related conditions are listed; the encephalitis and varicella items apply to acyclovir only):

  • Herpetic encephalitis
  • HZO/HSV involving V1 with potential corneal threat
  • Herpes zoster/HSV involving the sacral S2 dermatome, affecting excretion
  • Immunocompromised / cancer / transplant patients with herpes zoster or HSV
  • Varicella in neonates or immunocompromised patients
  • HZO/HSV-related keratitis or corneal ulcer
  • Acute retinal necrosis
  • Herpes zoster within 3 days of rash on head/neck/genital area — up to 5 days oral or topical

Duration cap (§10.7.1.1 point 3): "Except for the above specific conditions, treatment is limited to a 10-day course; oral, injectable and topical formulations must be used as a single agent — not combined."

Also: acyclovir 200 mg (Deherp), 400 mg, 800 mg (Virless) oral tablets used outside the above conditions are limited to a 7-day course.

Prescribing: this section requires no prior authorisation and does not restrict which specialty may prescribe; discuss the details with your doctor.

✅ §14.2 Topical acyclovir (restricted to)

  • HZO/HSV involving V1 with potential corneal threat
  • HZO/HSV-related keratitis or corneal ulcer
  • Acute retinal necrosis
  • Should not be combined with oral, topical or injectable preparations (i.e. ophthalmic acyclovir ointment is generally not used together with an oral antiviral)

⚠️ Key gap: ZEDS protocol vs Taiwan NHI rules

  • ZEDS uses valacyclovir 1000 mg/day × 1 year as chronic HZO suppression
  • Taiwan NHI §10.7.1.1 lists eye-related indications only as short-course treatment of specific conditions (keratitis, ulcer, V1 involvement, within 3 days of rash, etc.), does not list long-term suppression for HZO, and caps the course at 10 days in principle
  • So "1-year suppression" is NOT within Taiwan NHI's listed conditions. If your physician recommends it on individualised clinical grounds, it is typically out-of-pocket
  • This article does not decide for your physician whether you need long-term oral antiviral. Discuss with your ophthalmologist whether low-dose topical steroid maintenance is sufficient for your individual case, or whether oral suppression is still indicated

9. When to see your doctor immediately

ZEDS shows most SK was found at scheduled visits rather than at unscheduled visits for new complaints — that's why scheduled 3-monthly follow-up is the baseline. But if you develop any of the following, see your doctor same-day, not at the next scheduled visit:

🚨 Red flags for HZO patients

  • Sudden decline or blurring of vision (any degree)
  • Red, painful, light-sensitive, watery eye (especially within 3 months of stopping topical steroid)
  • Sudden floaters, flashes, visual field defect (possible acute retinal necrosis — rare but serious HZO complication)
  • New rash on the same forehead/upper eyelid/nose tip side as the original HZO — possible recurrence requiring immediate treatment
  • Corneal trauma / scratch history with pain or vision loss — denervated HZO corneas heal poorly

If any of the above, head to ophthalmology or general ER same-day. This article does not provide acute-management SOPs — let the on-site emergency clinician assess.

10. Conclusion: HZO is not a 7-day disease — it's a 7-year disease

HZO is easily mistaken for a "dermatology, 7-day antiviral and done" acute illness. The biggest message from ZEDS is the opposite: HZO ocular complications are chronic and relapsing, and most SK is found at scheduled visits. The Jacobs et al. 2026 SK secondary analysis offers a practical prescribing framework:

  • 3-month surveillance — 75% of SK was found at scheduled visits, not at extra visits for symptoms
  • Steroid maintenance and tapering require medical assessment. Some recurrent cases had recently stopped drops; this is not the recurrence rate among all who stopped.
  • Oral antivirals were newly added at event management in 11/105. This does not mean the others were not already taking them or that all HZO patients can omit antivirals. Treatment and tapering require individualized ophthalmic assessment.
  • Vision can be preserved — with active surveillance and avoiding abrupt cessation, most patients maintain near-20/25 acuity

If you or a family member has a history of HZO, even "everything seems fine now," please keep up with your ophthalmology follow-ups. That is the single most important reminder from the 527-patient, 18-month ZEDS dataset.

📚 HsiaoEye Related Articles — Cornea / Emergencies

References

  1. Jacobs DS, Lee T, Asbell P, Shen J, Choulakian M, Holland GN, Baratz KH, Prescott CR, Colby K, Hochman JS, Troxel AB, Cohen E, Jeng BH. Stromal Keratitis in the Zoster Eye Disease Study: Lessons Learned. Am J Ophthalmol. 2026;285:144–151. doi:10.1016/j.ajo.2026.01.034.
  2. Cohen EJ, Troxel AB, Liu M, et al. Low-dose valacyclovir in herpes zoster ophthalmicus: the Zoster Eye Disease randomized clinical trial. JAMA Ophthalmol. 2025;143(4):269–276.
  3. Liesegang TJ. Herpes zoster ophthalmicus natural history, risk factors, clinical presentation, and morbidity. Ophthalmology. 2008;115(2 Suppl):S3–12.
  4. Miserocchi E, Fogliato G, Bianchi I, Bandello F, Modorati G. Clinical features of ocular herpetic infection in an Italian referral center. Cornea. 2014;33(6):565–570.
  5. Sy A, McLeod SD, Cohen EJ, et al. Practice patterns and opinions in the management of recurrent or chronic herpes zoster ophthalmicus. Cornea. 2012;31(7):786–790.
  6. Lo DM, Jeng BH, Gillespie C, Wu M, Cohen EJ. Current practice patterns and opinions on the management of recent-onset or chronic herpes zoster ophthalmicus of Zoster Eye Disease Study investigators. Cornea. 2019;38(1):13–17.
  7. Cobo LM, Foulks GN, Liesegang T, et al. Oral acyclovir in the treatment of acute herpes zoster ophthalmicus. Ophthalmology. 1986;93(6):763–770.
  8. Hoang-Xuan T, Büchi ER, Herbort CP, et al. Oral acyclovir for herpes zoster ophthalmicus. Ophthalmology. 1992;99(7):1062–1070.
  9. Severson EA, Baratz KH, Hodge DO, Burke JP. Herpes zoster ophthalmicus in Olmsted County, Minnesota: have systemic antivirals made a difference? Arch Ophthalmol. 2003;121(3):386–390.
  10. Tran KD, Falcone MM, Choi DS, et al. Epidemiology of herpes zoster ophthalmicus: recurrence and chronicity. Ophthalmology. 2016;123(7):1469–1475.
  11. Liesegang TJ. Corneal complications from herpes zoster ophthalmicus. Ophthalmology. 1985;92(3):316–324.
  12. Mondino BJ, Farley MK, Aizuss DH. Sectorial corneal infiltrates and pannus in herpes zoster ophthalmicus. Graefes Arch Clin Exp Ophthalmol. 1986;224(3):313–316.
  13. Wilson A, Sharp M, Koropchak CM, Ting SF, Arvin AM. Subclinical varicella-zoster virus viremia, herpes zoster, and T-lymphocyte immunity to varicella-zoster viral antigens after bone marrow transplantation. J Infect Dis. 1992;165(1):119–126.
  14. Cohrs RJ, Mehta SK, Schmid DS, Gilden DH, Pierson DL. Asymptomatic reactivation and shed of infectious varicella-zoster virus in astronauts. J Med Virol. 2008;80(6):1116–1122.
  15. Pavan-Langston D, Yamamoto S, Dunkel EC. Delayed herpes zoster pseudodendrites. Polymerase chain reaction detection of viral DNA and a role for antiviral therapy. Arch Ophthalmol. 1995;113(11):1381–1385.
  16. Hu AY, Strauss EC, Holland GN, et al. Late varicella-zoster virus dendriform keratitis in patients with histories of herpes zoster ophthalmicus. Am J Ophthalmol. 2010;149(2):214–220.
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Frequently asked questions

Can herpes zoster ophthalmicus come back after treatment is finished?
Yes. The ocular complications of herpes zoster ophthalmicus are chronic and relapsing, and can flare again 5, 10 or more years later. The 5-year recurrence rate of eye disease or rash is about 25%, and in the ZEDS secondary analysis about 67% of patients with recurrent stromal keratitis already had stromal keratitis before or at enrollment, so it is not an acute illness that ends once treatment is done.
If my eye feels fine, do I still need regular ophthalmology follow-up?
Yes. The ZEDS secondary analysis showed that about 75% of recurrent stromal keratitis was detected by the physician at scheduled slit-lamp follow-up rather than at extra visits prompted by symptoms; symptoms were not recorded directly, but the authors take this to suggest that stromal keratitis needing treatment usually emerges without symptoms. Early inflammation often begins as a small sectorial infiltrate that the patient may not notice, but if untreated it spreads and leaves permanent scarring. No symptoms does not mean no inflammation, so scheduled follow-up is what catches it early.
What does recent steroid cessation among ZEDS recurrent cases mean?
In the ZEDS recurrence analysis, 18 of 48 people not using steroids at the event (38%) had stopped them within the preceding 3 months; this is not the recurrence rate among everyone who stopped. Treatment and tapering require individualized ophthalmic assessment.
Is a low-potency steroid eye drop less effective for long-term use?
ZEDS data support low-potency long-term maintenance. Among patients on a steroid at relapse onset, high- and low-potency users were split roughly evenly; however, this only compares the proportions of the two steroid types among people who had already relapsed and cannot show which better prevents relapse. When managing recurrence, about 88% of low-potency users were treated with an increase in dosing frequency only, without switching to high-potency; and low-potency is generally thought to carry a possibly lower long-term risk of raised eye pressure and cataract. Still, anyone on long-term steroid needs regular eye-pressure and lens monitoring.
Do I need long-term oral antiviral, and will Taiwan NHI cover it?
Oral antivirals were newly added at event management in 11/105. This does not mean the others were not already taking them or that all HZO patients can omit antivirals. Treatment and tapering require individualized ophthalmic assessment. Under the Taiwan NHI drug reimbursement rules (updated 2026-10-22), section 10.7.1.1, systemic anti-herpetic agents are limited to listed conditions (e.g. V1 involvement threatening the cornea, herpetic keratitis or corneal ulcer), courses are capped at 10 days in principle, and long-term suppression for HZO is not listed, so the 1-year suppression used in ZEDS is not within the listed conditions; if your physician recommends long-term use on individual grounds it is usually out-of-pocket.
What is the worst outcome if recurrent inflammation is not well controlled?
Long-term recurrent inflammation can cause new blood vessels to grow into the cornea, leave permanent scarring, and damage corneal sensation leading to neurotrophic keratopathy; the cornea may thin and become structurally unstable, and in rare cases progress to ulceration with perforation, eventually possibly requiring a corneal transplant. Conversely, with active surveillance, low-dose maintenance and avoiding abrupt steroid cessation, most ZEDS patients preserved vision near 20/25 — the reversible state this long-term strategy aims to protect.