Meibography imaging of the everted lids can be used to evaluate gland density, architecture, and degree of atrophy or dropout. (a) Moderate disease with gland shortening and partial dropout. (b) Severe disease with near total dropout
Evaporative dry eye and aqueous-deficient dry eye frequently co-occur, and as such, patients must be assessed for both . Ocular surface staining with vital dyes such as Lissamine green helps assess the degeneration of conjunctival and corneal epithelial cells and is a sign of late-stage disease. Fluorescein staining may also be used but will only pick up microerosions from areas of cell loss and exposed basement membrane. A low tear breakup time (TBUT) correlates well with MGD and shows the instability of the tear film. Patients with decreased TBUT often complain of rapid loss of clear vision between blinks and visual fluctuations.
Newer point of care testing for tear film analysis is now available as simple in-office tests to help guide diagnosis and treatment. Tear film osmolarity can be rapidly obtained using test cards with a minimal tear sample as part of the routine in-office workup for these patients. A tear film osmolarity score will help categorize the severity of dryness . Tear hyperosmolarity has been demonstrated to be an accurate indicator of dry eye as compared to traditional Schirmer’s testing . An osmolarity value of ≥308 mOsms/L or a variability of >8 mOsms/L between the eyes is significant for dry eye. Another rapid in-office tear film test looks for the presence of matrix metalloproteinase 9 (MMP-9) , an inflammatory cytokine that can be used as a biomarker to detect ocular surface inflammation. The high sensitivity and specificity for detection of elevated levels of MMP-9 (>40 mg/mL) in the tears of individuals with dry eye make this test valuable for identifying patients that may need the addition of an anti-inflammatory therapeutic .
Corneal sensation can also be tested preoperatively, especially in patients who are at risk for neurotrophic corneal disease, such as diabetics. These individuals have a higher likelihood of postoperative dry eye, as further damage to corneal nerves from surgery can exacerbate symptoms.
Fluorescein staining in this patient reveals 2+ inferior punctate corneal epithelial erosions and a TBUT of 3 s in both eyes. The tear film osmolarity test reads 318 mOsms/L OD and 307 mOsms/L OS, and InflammaDry testing demonstrates elevated levels of MMP-9 in both eyes. Meibomian glands are poorly expressible with 2–3 expressible glands per lid showing thickened “toothpaste”-like secretions. Meibography demonstrates significant truncation of meibomian glands with 50% gland dropout.
What Treatments Should Be Initiated in This Patient?
Treatment of MGD and blepharitis is particularly important prior to surgery. Blepharitis is a common cause of cataract surgery cancelation and is a major risk factor for postoperative endophthalmitis .
Treatment of MGD can be initiated with regular warm compresses at home. Expression of glands at home is often difficult to perform adequately especially in the elderly. Bacterial blepharitis should be cleared with the use of regular lid cleaning soaps. Baby shampoo is often used in clinical practice but can lead to skin irritation in some. In cases of Demodex mite infection, lid scrubs with the addition of a tea tree oil component can produce significant improvement . Patients need to be counseled not to use direct tea tree oil on the lids as it can cause severe burning and discomfort.
As warm compresses used at home often do not reach adequately high enough temperatures for enough time, the use of in-office thermal pulsation treatments are very beneficial in patients who are unable to achieve success with home therapy alone. At this time, the only FDA-approved system for thermal pulsation is LipiFlow (TearScience, Morrisville, North Carolina, U.S.A.), which is a 12-min procedure for heat and expression of the glands in-office .
Moderate to severe cases of lid margin disease can be managed with topical antibiotic ointments or oral tetracyclines . Doxycycline is particularly useful, not only for control of deleterious free fatty acids and bacterial overgrowth but also for its inhibition of tear film cytokines including, most notably, MMP-9 . Treatment with antibiotics will likely be required for at least 1 month before the patient has improved and is eligible for further cataract surgery evaluation . Increasing dietary intake of omega-3 fatty acids will also improve lid health by reducing inflammation and improving the quality of oil secretions from the glands .
Tear film inflammation can be further suppressed with short-term use of topical steroids. Although topical steroids have immediate effectiveness in decreasing tear film inflammatory cytokines, their long-term use is limited due to known side effects. In the preoperative setting, where rapid rescue and improvement of the ocular surface is needed, steroids may play an important role. Clinicians can therefore have a lower threshold for initiation of steroids in cataract surgery candidates with OSD than they would for other patients with dry eye. Long-term control of surface inflammation can be maintained with the use of topical cyclosporine A (CsA) . CsA 0.05% used twice daily with an adjunctive topical corticosteroid has been reported effective in managing dry eye patients in the cataract setting, with symptomatic and clinical amelioration in as few as 2 weeks . Newer anti-inflammatories targeting the specific inflammatory cascade in DES, such as lifitegrast, can also play an important role in long-term control of symptoms and signs of DES.
Aggressive lubrication with preservative-free artificial tears (PFATs) should be initiated in this patient. Preserved eye drops should be avoided—especially if used more than four times daily—as preservatives often promote further surface irritation and corneal damage . Autologous serum eye drops have also shown to significantly improve ocular surface punctate erosions and improve the tear film .
Before Cataract Surgery, What Preoperative Testing Should Be Performed in This Patient to Ensure Improvement and Stability in the Ocular Surface?
As light enters the eye, the most powerful refraction or bending of light occurs at the air-tear film interface. This is the point with the greatest change in refractive index from 1.00 in air to 1.34 in tear film . Montés-Micó estimated that small changes to the anterior radius of curvature of the tear film in DES can result in refractive power changes as high as 1.3 diopters . Individuals with a hyperosmolar tear film can have significant variability of repeated keratometry measurements, with corresponding variation in astigmatism and intraocular lens (IOL) power calculations . Hence, disturbances to the tear film in DES can interfere with refraction and potentially yield inaccurate preoperative measurements used for IOL selection and surgical planning. Stability of refractions, decrease in ocular surface staining, increase in TBUT, and normalization of the hyperosmolar and inflammatory marker tests in the tear film will be positive indicators of improvement.
Imaging modalities that can be used to assess tear film include topography and wavefront imaging. These tests are usually obtained during the workup of cataract or laser refractive patients and can be a first indication to the physician that there is irregularity of the tear film. The mires rings from the Placido images on topography can be irregular and show patches of missing rings when there is significant tear film disturbance. A Hartmann-Shack spot distortion can also be seen when trying to capture the wavefront image when there is tear film irregularity (Fig. 4.2). For optimal preoperative measurements, accurate biometry, and postoperative outcomes, these imaging tools can be used to ensure improvement of the tear film prior to proceeding with surgical planning.
A Hartmann-Shack spot distortion can be seen when trying to capture the wavefront image as a consequence of tear film irregularity
The patient discontinues saline eye drops and switches to lipid-based PFATs an average of six to eight times daily. He adheres to daily lid hygiene measures and begins treatment with topical cyclosporine 0.05% BID and oral doxycycline 50 mg BID. At a 1-month follow-up, signs of lid margin disease have significantly improved. However, topography ( Fig. 4.3 ) reveals tear film abnormalities with Placido disc rings demonstrating significant irregularities. After continuing therapy for an additional 6 weeks, repeat topography demonstrates smooth rings and regular corneal curvatures, and all other preoperative indices remain stable. Accordingly, the decision is made to schedule cataract surgery in the patient’s right eye.
Topography reveals tear film abnormalities with Placido disc rings demonstrating significant irregularities
What Intraoperative Considerations Should Be Taken into Account in a Patient with a History of OSD?
Various intraoperative measures can be taken to minimize surface damage and forestall the risk of postoperative dry eye. Anesthetic eye drop application and exposure to light from the operating microscope should be minimized. Use of light filters, delicate handling of the ocular surface, and avoidance of overly vigorous irrigation techniques may further mitigate the likelihood of postoperative dryness .
There is some evidence that the construction of grooved corneal incisions have been associated with persistent foreign body sensation, as well as pooling of mucus and debris in the groove . Cho et al. noted an increase in the severity of postoperative dry eye after grooved incisions compared to single-plane incisions . However, this was only significant in patients without pre-existing dry eye. The choice of incision architecture should be weighed against other important factors, such as the greater wound strength that can be achieved with grooved incisions. Additionally, a study by Donnenfeld et al. showed a decrease in corneal sensation in eyes that got limbal relaxing incisions at the 3 and 9 o’clock site that can result in worsening dry eye .
Femtosecond laser-assisted cataract surgery may also temporarily worsen postoperative dry eye symptoms when compared to conventional techniques . This may be related to the patient interface used, and various platforms may have varying degrees of impact on the conjunctival goblet cells. Long-term effects have not been studied, and therefore the choice to use a femtosecond laser to improve refractive outcomes can be weighed against this potential short-term worsening in the dry eye symptoms.
Successful conventional cataract extraction and monofocal IOL implantation is performed in the patient’s right. Corneal clarity is maintained throughout the case, and the patient tolerates the procedure well.
What Postoperative Measures Will Promote Ocular Surface Health?
Dry eye symptoms can worsen after cataract surgery—even in patients who have reestablished ocular surface health before surgery. Signs and symptoms of dryness tend to peak from as early as the first day through the first month postoperatively [4, 28]. Patients should continue therapy with PFATs, and individuals with MGD should maintain appropriate lid hygiene. The standard postoperative eye drop regimen may need to be modified in these patients. The use of preservative-free drops or newer formulations of NSAIDs and antibiotic drops with decreased ocular surface effects should be employed. As intracameral medications for cataract surgery develop and become mainstream, this postoperative drying effect from the preserved postoperative regimens may decline. Postoperative cyclosporine 0.05% twice daily, in particular, has been effective in limiting dry eye severity .
A postoperative regimen of prednisolone 1% and moxifloxacin 0.30% is prescribed for the patient; an NSAID eye drop is not used. Adjunctive cyclosporine 0.05% is continued. The patient continues the use of PFATs and lid hygiene measures. He is adherent to this postoperative regimen, though reports a mild increase in dryness, redness, and visual fluctuation during the first month. At his 1 month postoperative visit, uncorrected distance VA in the operated eye is 20/25. This VA remains stable over the first 6 months, and the patient is satisfied with the surgical result.
A 34-year-old woman with visually significant myopia is interested in LASIK. She has been a soft contact lens (CTL) wearer for the past 25 years. She uses daily-wear CTLs all day and sometimes sleeps in them. The patient reports worsening irritation with CTLs and no longer wishes to use them. In particular, she describes 3 months of persistent bilateral redness and frequent episodes of tearing, burning, foreign body sensation, and visual fluctuation. She recently saw another ophthalmologist, who recommended artificial tears and prescribed antivirals for presumed herpes simplex keratitis. Neither of these have alleviated her symptoms. Her past medical history is unremarkable, and she is taking no other medications. She is an attorney and spends the majority of the day working at a computer.
Her vision is poor without CTLs, and she prefers not to switch to glasses as her visual quality is not as good with glasses. You proceed to evaluate her as a candidate for LASIK. Uncorrected distance VA is 20/100 OD and 20/80 OS. BCVA is 20/20 OU. IOP is 14 mmHg OU. Slit lamp examination shows no lenticular opacities, and dilated fundus exam is unremarkable.
For a Chronic CTL Wearer with CTL-Related Discomfort, What Preoperative Considerations Should Be Taken into Account?
Long-standing CTL use may predispose patients to the development of various ocular surface disorders. Contact lens-associated keratopathy is a common cause of ocular surface disease in chronic CTL wearers. Timing of onset is highly variable among individuals, with cases occurring anywhere from 1 to 30 plus years after initiation of CTL use .
Chronic CTL wear may alter corneal metabolism and physiology as a result of injury to limbal stem cells (LSCs) . LSCs are required for normal corneal epithelial cell turnover and repair of epithelial defects. However, CTLs can create a hypoxic environment, resulting in limbal stem cell strain and dysfunction with subsequent epithelial instability. Poorly fitting lenses may lead to additional mechanical irritation at the limbus and cause further damage to the stem cell population . Chronic inflammation likely plays a role in limbal stem cell dysfunction (LSCD) from CTL overwear .
Pre-LASIK evaluation of this patient for LSCD is imperative. Irregularity of the corneal epithelium can result in instability of refractions and incorrect treatment measurements. Furthermore, wound healing requires proper LSC health and function to allow a smooth reepithelialization of the ocular surface. In addition, because LSCD predisposes individuals to corneal erosions or abrasions, these must be ruled out before surgery.
Prolonged CTL wear may also promote or exacerbate dry eye syndrome (DES) , particularly in individuals with subclinical or pre-DES. DES is the most common reason for CTL intolerance and discontinuation . Ocular irritation and discomfort in this patient may therefore be a sign of chronic dry eye. Though the exact mechanisms of CTL-associated DES are unknown, potential causes include chronic inflammation, hypoxic environment, corneal hyposensitivity, and adverse reaction to lens solution [34–37]. Subsequent tear film insufficiency increases the risk of corneal damage, and the resulting inflammation exacerbates both dry eye and LSCD. Reduced healing capacity secondary to LSCD further increases risk of corneal injury and inflammation, promoting a vicious cycle. DES certainly worsens in patients following LASIK , and as such, this patient must be thoroughly evaluated and treated for dry eye disease before undergoing surgery.
Preoperative pachymetry and corneal topography evaluation are essential in all LASIK candidates and are particularly relevant in chronic CTL wearers. Long-term use of CTLs often alters corneal topography—a phenomenon that was historically exploited by practitioners of orthokeratology. Continuous CTL wear can increase central and peripheral corneal thickness within periods as short as 30 days . Further, CTL-induced warpage may mask subclinical keratoconus, and artificially thick pachymetry measurements prior to LASIK may increase the risk of postoperative ectasia .
What Symptoms in This Patient Elevate Your Suspicion for Limbal Stem Cell Strain or Deficiency?
Patients with LSCD often have nonspecific complaints of irritation, with symptoms similar to those of DES . LCSD and DES cannot be differentiated based on symptomatology alone, and the patient may demonstrate elements of both conditions concurrently. Individuals with mild or partial LSCD may be asymptomatic. As the deficiency progresses, however, patients can present with chronic redness, tearing, burning, foreign body sensation, blepharospasm, and visual fluctuation. LSCD can predispose to persistent epithelial defects or recurrent epithelial erosions and abrasions, which can lead to severe pain, photophobia, and further compromise visual acuity. These features can masquerade as herpes keratitis. This particular patient’s failure to improve with antivirals, however, renders herpes keratitis less likely. Importantly, treatment with topical antivirals can cause further insult to LSCs and thus exacerbate symptoms.
How Do You Diagnose OSD in a Chronic CTL Wearer?
Clinical examination of these patients should involve multiple modalities. Slit lamp biomicroscopy with fluorescein staining may reveal characteristic, albeit nonspecific, features of LSCD. Late fluorescein staining may be apparent secondary to loss of intercellular tight junctions with subsequent basement membrane staining. A whorled epithelial keratopathy can be seen at the superior and inferior limbus, and severe cases can extend into the visual axis and cause significant visual dysfunction (Fig. 4.4). Other typical features that may be apparent early in the course of LSCD include conjunctival hyperemia and a loss of limbal architecture with obscuration of the palisades of Vogt . The superior limbus may be more susceptible to mechanical rubbing or hypoxia from CTLs, and as such, focal LSCD is more common superiorly than inferiorly .
As a consequence of limbal stem cell deficiency , (a) a whorled epithelial keratopathy can be seen in the visual axis approaching from the limbus, and (b) loss of normal limbal architecture with invading neovascularization can be visualized
Limbal stem cells serve as a physiologic barrier separating the cornea from adjacent conjunctiva. Disruption of this barrier may therefore result in conjunctivalization of the cornea. Early on this may be seen as an opaque sheet of cells indicating encroachment of conjunctival tissue onto the corneal surface and later may develop into superficial vascularization onto the peripheral cornea . In severe disease, a fibrovascular pannus can result in corneal scarring or keratinization of the ocular surface. Mild LSCD typically demonstrates focal or sectoral corneal involvement, whereas advanced disease can affect most or all of the corneal surface.
Advanced LSCD is often characterized by the presence of poorly healing or recurrent epithelial erosions; ulceration, melting, and perforation can also occur . CTL-induced keratoconjunctivitis resembling superior limbic keratoconjunctivitis can also be a sequela of long-term CTL use .