Pressure-induced interlamellar stromal keratopathy (PISK) is a rare complication that can occur following corneal lamellar surgeries such as laser-assisted in situ keratomileusis (LASIK), small-incision lenticule extraction (SMILE), and corneal inlays.1
It is characterized by fluid accumulation within the interface, or the space created by the laser that separates the cornea into both anterior and posterior stromal beds.1 To provide optimal post-surgical co-management, it is critical that optometrists are educated on this condition.
An overview of pressure-induced interlamellar stromal keratopathy
PISK was first described in 2002 as a subcategory of interface fluid syndrome (IFS), aptly named for any amount of fluid accumulation within the interface with various causes such as uveitis, endothelial decompensation, or a steroid-induced rise in intraocular pressure (IOP).2-3
The fluid accumulation in PISK, also called a fluid cleft, is secondary to elevated IOP within the anterior chamber, often caused by chronic topical corticosteroid use. Patients with PISK present with blurred vision and diffuse corneal haze that is often misdiagnosed as corneal inflammation.2-3
The original proposed term for PISK was pressure-induced stromal keratitis, but studies using confocal microscopy revealed that no keratocyte inflammation was present in the interface fluid.4-6 This idea is supported clinically by the fact that PISK is worsened by topical corticosteroid use and resolves with their discontinuation.
PISK risk factors
Risk factors for developing PISK include a history of lamellar surgery (LASIK, SMILE, corneal inlays) and an increased susceptibility to a steroid-induced rise in IOP. This includes patients with primary open-angle glaucoma (POAG), type 1 diabetes mellitus, connective tissue disease, and high myopia.7
Although it is a rare condition only impacting 1 out of every 2,500 LASIK patients, early recognition of PISK is imperative to avoid significant vision loss associated with sustained elevated IOP.8
Differential diagnoses for PISK
Diagnosing PISK can be challenging as it is very commonly misdiagnosed as inflammation or infection.
Diffuse lamellar keratitis
Diffuse lamellar keratitis (DLK) or “Sands of the Sahara” is an early, post-operative complication characterized by whitish, granular, focal or diffuse inflammation within the corneal interface and stroma.9
The most common cause of DLK is contaminants introduced into the interface during surgery, such as bacterial endotoxins, chemicals, or foreign particles, though trauma can also stimulate the condition.9 It is most often diagnosed at the one-day post-operative exam and is often mistaken for other conditions such as infections, central toxic keratopathy (CTK), and PISK.4
DLK is characterized into four stages of severity:4
- Stages 1 and 2
- Present as mild, focal inflammation
- Responds well to frequent topical corticosteroid treatment
- Stages 3 and 4
- Severe, diffuse inflammation
- Requiring surgical intervention, such as flap lifting and irrigation
It is uncommon for patients to experience foreign body sensation, pain, or a decrease in vision in the early stages.4 DLK is diagnosed most often on post-operative day one, and PISK occurs only after a patient develops a rise in IOP, which is often secondary to use of topical corticosteroids, and, on average, occurs after at least 2 weeks of corticosteroid use.10
Pearl: While both PISK and DLK can present with what appears to be a hazy cornea, inflammation is the culprit with DLK and is not in PISK.
Microbial keratitis
Microbial keratitis is a differential for PISK as it is considered the most sight-threatening complication of lamellar surgery. It is an infection within the interface that presents with dense, gray-white corneal infiltrates with indistinct margins and conjunctival hyperemia.4
Early-onset microbial keratitis occurs within the first 2 weeks following the procedure and is commonly caused by gram-positive organisms, the most worrisome type, methicillin-resistant S. aureus (MRSA).4 Late onset occurs after 2 weeks and up to 3 months post-operatively and is may be caused by atypical mycobacterial and fungi.4
Risk factors for development include blepharitis, dry eye, intra-operative contamination, and use of topical corticosteroids.4 Patients will report a foreign body sensation and pain, photophobia, redness, and decreased vision. Prompt management with antibiotics is necessary and often requires culture and lab diagnosis.4
Pearl: PISK is unlikely to present with pain and photophobia and will have a diffuse corneal haze vs. the corneal infiltrates seen with microbial keratitis.
Diagnostic testing and imaging for PISK
IOP
A key diagnostic feature of PISK is the discrepancy between the IOP measured on the central cornea and that measured peripherally outside of the LASIK flap or treatment zone.
In patients with PISK, the IOP measurement of the central cornea with Goldmann applanation tonometry (GAT) will be artificially lower as this method is instead measuring the pressure gradient of the fluid in the interface instead of the high pressure of the anterior chamber.11
It is possible to measure the IOP outside of the LASIK flap with GAT by instructing the patient to look up or to the side, but the peripheral cornea in contact with the tonometer is thicker than the central cornea and may lead to an overestimation of the pressure.
iCare
Previous studies have shown that rebound tonometry (iCare) is a more accurate way to measure IOP in patients with PISK.11-12 This method measures the rebounding velocity of the probe, which occurs only after the probe is stopped by the pressure of the anterior chamber and corneal endothelial interface.11
This technique is likely more reliable than applanation methods for diagnosing PISK, and can be used to precisely measure both the central and peripheral cornea. With PISK, it is not uncommon for the IOP measured peripherally to be 10 to 20mmHg higher than the IOP measured centrally.11
Slit lamp exam
Detecting the clinical signs of PISK quickly is imperative to avoid ocular complications caused by extended periods of raised IOP. One of the first characteristics noted by the eyecare practitioner is diffuse corneal haze found during slit lamp biomicroscopy.
Further examination with an optic section may reveal the presence of a thin, black fluid cleft in the interface, oftentimes seen in more advanced cases.12
Figure 1: Anterior segment photo shows a thin, black fluid cleft at the level of the LASIK interface in a patient who has advanced PISK.
Figure 1: Courtesy of Lily Arendt, OD, FAAO.
Figure 2: Magnified image of the fluid cleft in Figure 1.
Figure 2: Courtesy of Lily Arendt, OD, FAAO.
Anterior segment OCT
Early within the disease state, a fluid cleft on slit lamp examination may not be detectable to the human eye. Anterior segment optical coherence tomography (AS-OCT) can instead be used to help diagnose early cases of PISK.
The AS-OCT scan through the central cornea will reveal a hyporeflective space in the region of the interface representing an accumulation of fluid between the interface and the posterior stromal bed.13
Figure 3: AS-OCT through the central cornea, revealing a black space in the LASIK interface of both the (a) right eye and (b) left eye representing an accumulation of fluid between the LASIK flap and the posterior stromal bed in both eyes.
Figure 3: Courtesy of Lily Arendt, OD, FAAO.
Figure 4: Pre-LASIK tomography of a right eye in a -5.00D myope reveals a cornea with with-the-rule astigmatism and a minimum corneal thickness of 509μm.
Figure 4: Courtesy of Lily Arendt, OD, FAAO.
Figure 5: Post-LASIK tomography of a right eye reveals a cornea myopic ablation pattern and a minimum corneal thickness of 505μm when the expected post-LASIK minimum corneal thickness should be around 430μm after treating 5.00D of myopia, suggesting that there is edema present.
Figure 5: Courtesy of Lily Arendt, OD, FAAO.
Corneal pachymetry
Corneal pachymetry can be helpful not only for the diagnosis of PISK, but also for following its resolution over time. Corneal thickness can be measured using either a corneal pachymeter or a corneal tomographer.
It is particularly helpful to use corneal tomography to compare corneal thickness pre-surgery to post-surgery in your PISK patients to confirm that the post-surgery thickness matches the predicted value for their pre-surgery prescription, as shown in Figures 4 and 5.
For example, a patient who is -5.00D prior to LASIK with a minimum corneal thickness of 509μm would likely have a minimum corneal thickness of around 430μm following the surgery. If the corneal thickness is higher than expected in a patient with blurred vision and corneal haze, there is likely interface edema present.
Treatment of PISK
As inflammation is not the cause of PISK, the addition of corticosteroids will not resolve the condition and is likely to exacerbate it. The correct treatment is to eliminate the cause of the steroid-induced elevated IOP and lower the IOP.
Both topical and oral ocular hypotensive medications can be used if there are no contraindications. The patient should be monitored closely with IOP measurements and corneal pachymetry until resolution of visual symptoms.
If the patient is unhappy with their vision following fluid resolution, it is recommended to refer the patient back to their surgeon for a possible surgical enhancement.
Key takeaways
- Consider PISK on your list of differentials for all patients who have undergone corneal lamellar surgery and have new-onset blurred vision with concomitant corticosteroid use.
- Make sure to check IOP centrally and peripherally outside of the LASIK flap or treatment zone with rebound tonometry to reveal the elevated IOP causing PISK.
- Obtain pre-surgical corneal tomography scans on all patients that you are referring for corneal lamellar surgeries, so that you can have data in which to compare if new visual symptoms arise.
- Use anterior segment OCT to help reveal fluid accumulation in the interface for patients with milder cases of PISK who don’t present with a fluid cleft on slit lamp examination.
- Topical corticosteroids—while incredibly useful—are not the solution for all hazy corneas. Resolution of PISK requires a discontinuation of steroid use and the initiation of ocular hypotensive drops.
