Herpes simplex virus stromal keratitis and endotheliitis after femtosecond laser–assisted cataract surgery and astigmatic keratotomy

Chou, Timothy Y. MD; Lisa, Anthony MS; Nuzbrokh, Yan BS; Mauro, John DO; Gang, Anjulie MD

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doi: 10.1097/j.jcro.0000000000000040
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Femtosecond laser–assisted cataract surgery (FLACS) has become an increasingly popular alternative to conventional cataract surgery. The femtosecond laser (FSL) can be used to accomplish several key initial steps of cataract surgery, including creation of corneal-relaxing incisions.1,2 With ultrashort pulses and minimal collateral tissue damage, femtosecond laser astigmatic keratotomy (FSAK) can be performed with greater precision and efficacy than manual incisions.1,2 Although generally safe, FSL procedures still have the potential to be complicated by secondary microbial infection, including herpes simplex virus (HSV) reactivation.3,4


A 72-year-old woman underwent uneventful FLACS in the right eye, combined with superonasal and inferotemporal FSAK incisions. Everything looked satisfactory on the first postoperative day. Two weeks later, however, the patient developed pain and decreased vision in her operative eye. Slitlamp examination revealed ulceration and infiltration in the superonasal cornea, at one of the astigmatic keratotomy (AK) sites. There was a dense fibrinous anterior chamber reaction, generating concern for impending endophthalmitis. The patient was, therefore, tapped and then injected with intravitreal antibiotics. She was started on topical fortified vancomycin and tobramycin and a low topical steroid dose. Although there was improvement of the anterior chamber inflammation, the infiltrate did not resolve; 6 weeks postoperatively, with negative cultures, topical voriconazole and oral ketoconazole were empirically added to the therapeutic regimen. Later, the patient was also placed on doxycycline, and at one point, a cryopreserved amniotic membrane ring was placed. Eventually, the ulcer healed, but corneal inflammation and infiltration persisted. Antibiotic and antifungal eyedrops were continued on maintenance dosing, without much further clinical change.

At 4.5 months postoperatively, the patient was referred to our university corneal service for another opinion about the perisistent keratitis. At the time of evaluation, the patient complained of distorted vision, photophobia, and intermittent sharp pains in the right eye. She had had no ocular history of corneal or eye infection. On examination, corrected distance visual acuity was 20/50-2. Corneal sensation was decreased. A thickened pannus was observed at the slitlamp, extending 3.0 mm into the superonasal cornea (Figure 1). The epithelium was intact. Underneath the pannus were deeper vessels, at the proximal end of which appeared to be an intrastromal lipid infiltrate. Above the lipid was diffuse stromal haze, surrounding the FSAK incision. There was 40% stromal thinning proximal to the pannus, and Descemet folds were present, radiating from the superonasal to central cornea. The folds were dotted with keratic precipitates. HSV stromal keratitis and endotheliitis was suspected based on clinical examination and unsuccessful response to topical fortified antibiotic and antifungal medications. Empiric treatment was initiated with topical loteprednol 0.5% 3 times a day and 1 g of oral valacyclovir 2 times a day.

Figure 1.
Figure 1.:
Slitlamp photograph showing stromal keratitis in superonasal right cornea, surrounding and obscuring original femtosecond laser astigmatic keratotomy incision.

Over the course of the next 3 weeks, topical steroid drops were tapered as the keratitis improved. The corneal vessels regressed, the lipid infiltrate resorbed, and the radiating corneal folds resolved. Residual superotemporal corneal thinning remained. Corrected distance visual acuity eventually improved to 20/25 in the right eye. Oral valacyclovir was recommended to be continued, as prophylaxais against recurrence.


Ocular HSV infection has developed after a variety of ophthalmic surgeries and laser procedures, with varying clinical manifestations. HSV dendritic keratitis was observed after FSAK, appearing around one AK incision and then the other.3 Reactivation of epithelial disease as well as a case of herpetic endophthalmitis have occurred subsequent to conventional cataract surgery5,6 Epithelial and stromal herpes simplex virus keratitis (HSK) have both been documented after excimer laser photokeratectomy and phototherapeutic keratectomy.4,7 We believe, to our knowledge, this case to be the first report of HSV stromal keratitis, endotheliitis, and uveitis after FLACS + FSAK. A not-dissimilar case of necrotizing herpetic keratouveitis ensued after microkeratome-assisted laser in situ keratomilieusis.8

We believe that our patient likely initially presented with a necrotizing HSK and uveitis, something that can masquerade as other types of infection. In time, it evolved into more of a stromal interstitial keratitis and endotheliitis. Although topical steroids were later useful to resolve our patient's keratitis (which probably had become immunologic by the time she presented to us), steroid eyedrops arguably could have fueled the keratouveitis when it first appeared.1,8

HSK has been known to reactivate after excimer laser ablations of the cornea.3,7,9 The excimer laser emits radiation of 193 nm wavelength (ultraviolet [UV]-C), which is in the UV spectrum.7 UV radiation seems to trigger HSV reactivation.7,9 Studies have shown that UV light at this wavelength is almost completely absorbed by the presented ocular target, inducing photodisruption of intermolecular bonds.7 The exact mechanism by which local trauma affects latent virus within the ganglion in a retrograde manner is unknown. It has been proposed that, in addition to exposure to energy in the UV light wavelength, severe damage to the trigeminal nerve plexus in the deeper subepithelial stroma and topical steroid use might all be required to induce HSK activation after excimer laser treatment.5,7,9 Regarding FSL, radiation is emitted in the near-infrared wavelength.1,10 It is unclear whether HSK activation after FSL is in any way specifically related to the laser wavelength. Tissue trauma alone, leading to secondary inflammation, seems to be sufficient to promote HSV recurrence in animal models.11 During cataract surgery, pretreatment with the FSL seems to elevate aqueous prostaglandin levels.12 HSK recurrences have incidentally been reported in association with use of topical prostaglandin agents for glaucoma.13 Prostaglandins have been proposed to be a key component of an inflammatory cascade that might promote HSV recurrence.11,13,14 We speculate that the penetration of the photodisruptive FSL energy deep into the corneal stroma from creation of an AK might, as with the excimer laser, damage stromal nerve endings. Adding further putative triggers such as postoperative inflammation with prostaglandin release and topical corticosteroid use resulted in HSK reactivation in our patient.

Our patient did not have a known history of HSK and, yet, still developed herpetic keratitis post-FLACS + FLAK. The percentage of people who show HSV seropositivity approaches 100% by age 60 years or older, which happens to be the age of most patients for cataract surgery.15 We, therefore, suggest that patients undergoing FLACS or FLAK be counseled preoperatively about possible reactivation of HSK. Surgeons might wish to consider systemic antiviral prophylaxis or even avoid use of the FSL altogether in patients with actual history of HSK.


  • Herpes simplex virus (HSV) keratitis can reactivate after a number of ophthalmic surgical and laser procedures. Stromal HSV keratitis has occurred after excimer laser surgery, and epithelial HSV keratitis has developed after conventional cataract surgery and after femtosecond laser arcuate keratotomy.


  • This report presents, to our knowledge, the first case of HSV stromal keratitis and endotheliitis after femtosecond laser–assisted cataract surgery combined with astigmatic keratotomy. It adds to knowledge about uncommon infectious complications associated with such procedures and proposes both etiologic factors and preventative actions.


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