Diffuse lamellar keratitis, toxic syndrome, and GAPP syndrome

Diffuse lamellar keratitis (DLK) is a whitish, granular, culture negative, inflammatory response of the corneal lamellae that occurs in the early postoperative period in 0.67% of cases. Although still unclear, contaminants introduced in the lamellar interface during surgery, epithelial defects, and femtosecond laser may trigger the inflammatory cascade. Late-onset DLK has also been reported associated with epithelial defects, reactivation of herpetic keratitis, or viral keratoconjunctivitis10 DLK may cause scarring and visual loss11.

Prompt diagnosis and treatment are essential to avoid visual sequelae. The cellular reaction in the interface is usually apparent in the first 24 hours, and starts at the periphery of the lamellar flap5,11. It is important to differentiate DLK from punctate epithelial keratopathy (stains with fluorescein), or the presence of meibomian gland or tear film debris that become trapped under the flap (yellowish appearance).

Stages 1 (white granular cells in the periphery of the flap, with sparing of the visual axis) and 2 (involving the visual axis in ‘sands of the Sahara’ appearance) require hourly topical steroids (prednisone) and daily monitoring. Most cases resolve in 7–10 days (Fig. 27.2A). Steroid-induced glaucoma may occur. If a pocket of fluid develops in the lamellar interface due to the increased IOP, the measurement of IOP by central Goldmann applanation tonometry appears falsely low, and IOP should be confirmed in the periphery of the cornea11.

Fig. 27.2 (A) Stage 2 Diffuse lamellar keratitits (DLK). Whitish inflammatory reaction located in the interface that involves the visual axis. The ‘sands of the Sahara’ appearance is seen. (B) Differential diagnosis between DLK and infections. Infections after LASIK often present with focal infiltrates and inflammation in the corneal interface. Treatment with topical vancomycin and clarithromycin was started.

In 1/500 cases, the inflammation progresses despite treatment to Stage 3: denser aggregation of white cells in the visual axis with clearing in the periphery. Untreated Stage 3 DLK results in visual loss due to permanent scarring. Lift the flap and irrigate the interface with BSS with a blunt canula to debulk the inflammatory reaction. Avoid aggressive scraping of the flap or stromal bed with bladed instruments. Taper topical steroids as the cellular reaction resolves. Rarely, stromal melting, permanent scarring, and visual loss develop (Stage 4). Avoid lifting and irrigation at this point as it may result in additional tissue loss.

GAPP (Good acuity plus photophobia) syndrome or most commonly known as TLS (“transient light sensitivity”) is a reaction of unknown origin related to femtosecond laser that usually appears 2–6 weeks after uneventful LASIK. An inflammatory base is suspected as it resolves within 1 week of steroid treatment.

Sonmez and Maloney described a new syndrome of unknown cause associated with excimer laser ablations (PRK and LASIK), the ‘toxic syndrome’: a non-inflammatory central corneal opacification with a significant hyperopic shift. The opacification gradually clears over a period of 2–18 months, leaving the eye hyperopic (more than +2D). Enhancement is indicated to treat residual hyperopia and remove residual striae. Corticosteroid treatment is not indicated12.

Infections

Infections after excimer laser surgery are very rare (0.02–1.5%), but may lead to moderate to severe visual loss in up to 49.4% of the eyes affected. Early-onset infections (≤7 days of surgery) occur in 49.4% of cases, and are generally caused by Gram-positive bacteria (S. aureus), whereas late-onset infections (≥10 days after surgery) represent 50.6% of cases, and are mainly caused by atypical mycobacteria (Mycobacterium chelonae) (Fig. 27.2B). Fungal infections are less frequent (up to 20% of late-onset cases), but may cause extremely severe infections that may end up in endophthalmitis and severe visual loss. Sources of infection include patients’ eyelids, surgical instruments, and postoperative inoculation by the patient.

Infections after LASIK present with infiltrates and inflammation in the corneal interface (virtual space where any cell tends to accumulate). Differential diagnosis with DLK is sometimes arduous. Infections are suspected with the appearance of interface inflammation more than 1 week after LASIK, the presence of focal infiltrates, corneal flap and epithelium involvement, and the absence of response to topical corticosteroids. Melting of the lamellar flap may occur in up to 13.3% of cases.

Promptly start with topical, broad-spectrum antibiotics. No significant relationship between systemic antibiotic use and final visual outcome has been demonstrated. If no response or worsening is observed despite 7 days of treatment, consider the possibility of a fungal infection.

As antibiotic penetration to the interface is limited, lifting of the flap for antibiotic irrigation, scraping of the interface for culture, and repositioning of the flap are recommended. However, flaps may be therapeutically removed when they are considered to be the source of infection, or important melting is seen. Almost 60% of such cases had moderate or severe visual loss.

Therapeutic penetrating or lamellar keratoplasty is rarely required. The main indications are: persistent, worsening infiltrate despite 2–12 weeks of medical therapy, progressive, uncontrolled corneal thinning or perforation, and scarring and irregular astigmatism13.