Chapter 4

Jodi Luchs, MD, FACS

Cataract surgery is one of the most common surgical procedures performed in the United States.^1,2,3 Over the past several decades, there have been major advances in technology surrounding cataract surgery: from newer, more advanced pharmaceuticals and topical anesthesia, to femtosecond laser–assisted cataract surgery and advanced technology toric and presbyopic lens implants. These advances, and others, have elevated cataract surgery to the level of precision and recovery commonly associated with refractive surgery.

Similarly, there are approximately 700,000 refractive surgical procedures performed annually in the United States.⁴ Refractive surgery, like cataract surgery, has evolved significantly over the years with the advent of eye tracking, custom wavefront-guided/wavefront-optimized procedures, iris registration, and femtosecond laser flap creation. These advances have greatly enhanced the precision, optical outcome, and speed of recovery from refractive surgery.

With patients now expecting to recover from ocular surgery and be glasses-free within hours of their procedure, it has become essential to pay close attention to every aspect of the surgical process, beginning with the preoperative evaluation. Critically important are the health and integrity of the tear film and ocular surface.

The tear film is the very first refracting surface of the eye. Incoming light must pass through a pristine, uniform, and undisturbed tear film as a first step toward proper focus on the retina. Approximately two-thirds of the eye’s optical power is derived from the cornea—including the tear film—and the greatest change in refractive index occurs between air and the tear film.⁵ Any disruption to the uniformity, optical clarity, spreadability, and longevity of the tear film on the ocular surface will disturb this process, often with untoward effects on vision and recovery from ocular surgery.

When the tear film becomes unstable or irregular, variations in optical power may occur, which can induce significant higher-order aberrations. Patients may report symptoms of diplopia, starbursts, glare, and shadowing.5 While blinking can temporarily restore the tear film in these cases, between blinks the tear film degrades and once again becomes irregular. Studies have demonstrated that increased light scatter in patients with dry eye worsens image quality.⁶ Similarly, image quality has been shown to be highest immediately after a blink, and image quality degradation and higher-order aberrations develop more quickly between blinks in dry eyes compared with normal eyes.^7,8

In an era when patients spend more time viewing handheld mobile devices, tablets, and computer monitors—all of which reduce blink rate—dry eye has become more prevalent.

An unstable tear film and ocular surface poses a wide range of potential problems for the surgical patient and can negatively impact multiple aspects of the surgical process including preoperative measurements, intraocular lens selection, the surgical procedure itself, postoperative recovery, and the development of symptomatic postoperative dry eye.

Accordingly, it is crucial to focus on the health and integrity of the ocular surface and tear film in our patients about to undergo ocular surgery.

CAUSES OF AN UNSTABLE TEAR FILM

Ocular surface diseases such as dry eye, blepharitis, and ocular allergy are the most common causes of an unstable tear film, which can affect ocular surgery.

Dry Eye

Aqueous-deficiency dry eye reduces the tear volume and spreadability and is associated with increased osmolarity. Both reduced tear volume and increased osmolarity can produce ocular surface damage, which can disrupt the normal smooth contour of the ocular surface. Clinically, this is evidenced by fluorescein and lissamine green staining as a marker for ocular surface damage and irregularity. Dry eye has been associated with increased light scatter within the eye, which can be improved with lubrication.⁹

Blepharitis

Blepharitis commonly presents in anterior and posterior forms. Anterior blepharitis is often associated with an overgrowth of gram-positive bacteria on the lid margins. Clinically, this condition is associated with crusting at the base of the lashes (colarettes), and even ulceration of the lid margin in severe cases. The excessive gram-positive bacteria on the lid margins triggers inflammation on lids and ocular surface, which may result in the release of inflammatory cytokines in the tear film, producing instability or ocular surface damage. In addition, the increased bacterial load on the lid margins may increase the risk of postoperative infection¹⁰ if not addressed preoperatively.

Posterior blepharitis is associated with inflammation within and surrounding the meibomian glands, which can alter the composition and clinical characteristics of the meibomian gland secretions. These secretions form the lipid layer of the tear film, which is responsible for promoting proper spreading of the tears on the ocular surface as well as retarding evaporation. In the presence of posterior blepharitis, both the quality and the quantity of these lipid secretions is altered, thereby producing an unstable tear film that may not spread properly and evaporates rapidly. This can be identified clinically by a rapid tear film breakup time. In addition, the evaporative tear loss can increase tear film osmolarity and directly and indirectly lead to ocular surface damage.

Ocular allergy, along with dry eye and blepharitis, is a common ocular surface disease. When allergens in the air dissolve in the tear film of susceptible individuals, they initiate an inflammatory cascade within the conjunctiva that begins with the release of histamine and other inflammatory mediators from mast cells. These inflammatory mediators in the tear film produce destabilization and facilitate the recruitment of additional inflammatory cells into the conjunctiva, which then release additional inflammatory mediators. This cycle of inflammation, especially in those who suffer from chronic ocular allergy, may produce an unstable tear film and lead to ocular surface staining. Patients suffering from ocular allergy have been shown to have a higher incidence of dry eye,11,12 contact lens intolerance,¹³ diffuse lamellar keratitis after LASIK,¹⁴ and haze and regression following photorefractive keratectomy.¹⁵ In addition, patients suffering from ocular allergies often take oral antihistamine medications, which can worsen dry eye, further destabilizing the ocular surface.

SURGICAL PATIENTS ARE AT RISK

Patients seeking cataract and refractive surgery are already at higher risk for ocular surface disease. Refractive surgical patients are self-selected for dry eye and ocular surface disease, often seeking refractive surgery because they are unable to tolerate contact lenses. Many of these patients have been long-term contact lens wearers, which increases the risk of concomitant dry eye and meibomian gland dysfunction.^16–18 Patients seeking cataract surgery are usually older and experiencing hormonal changes, whether they are perimenopausal women or men with reduced testosterone levels. Patients in this demographic are generally taking more systemic medications, many of which may dry the ocular surface, further increasing their risk. These patients are often marginally compensated prior to surgery, and the increased corneal anesthesia produced by the surgical procedure may convert them into overtly symptomatic disease.

However, it is easy to overlook ocular surface disease in these patients, as our attention is primarily focused on the refractive error (in the case of refractive surgical patients) or the cataract as the cause of the patients’ visual complaints. After surgery, however, the ocular surface disease will remain, and may be potentially exacerbated, thereby impacting surgical recovery and the patient’s ultimate outcome and satisfaction. One study by Luchs et al found that up to 59% of patients evaluated at the time of their biometry for cataract surgery had clinical signs of blepharitis, and 36% of those with blepharitis had tear film breakup time of 5 seconds or less.¹⁹ Another study by Trattler et al²⁰ found that 80% of patients presenting for cataract surgery had clinical signs of International Task Force on Dry Eye level 2 or higher, with only 22% of patients having a previously known diagnosis of dry eye. Both of these studies suggest that dry eye and blepharitis are very common in our cataract surgical patients, often producing a clinically significant tear film disturbance, yet are frequently overlooked by clinicians.

Both refractive surgery and cataract surgery can produce dry eye postoperatively,15–17 even without the presence of ocular surface disease preoperatively. However, the presence of any of these conditions preoperatively will worsen any postoperative dry eye, illustrating the importance of identifying and treating the condition preoperatively.

SPECIFIC EFFECTS OF OCULAR SURFACE DISEASE ON OCULAR SURGERY

Preoperative Measurements

The irregular and unstable tear film from ocular surface diseases can significantly impact the accuracy, repeatability, and reliability of many of the instruments we use to evaluate our patients preoperatively and upon whose data we make surgical decisions. Keratometry and Placido-based corneal topography rely upon reflections from a stable tear film on the ocular surface in order to generate their data. Tear film instability can significantly impact the reliability of these results. Similarly, unstable tear film will alter the accuracy of manual or automated refractometry, optical biometry, and the wavefront analysis of optical aberrations within the eye. Wavefront aberrations have been demonstrated to increase in the presence of dry eye and increasing tear film osmolarity.^9–11

The consequences of these inaccurate measurements can be significant. Errors in preoperative keratometry or optical biometry can lead to errors in intraocular lens calculations, which may produce an off-target, postoperative refractive “miss.” This can be particularly problematic in patients receiving a multifocal implant when the defocus curves drop off significantly with uncorrected refractive errors above 0.5 diopters. Similarly the magnitude or axis of toric intraocular lenses may be affected by inaccuracies of preoperative keratometry. Errors in preoperative wavefront or topography measurements may alter refractive surgical planning, thus affecting refractive outcomes in these patients as well.

Intraoperative Surgical Implications

While most of the ramifications of untreated ocular surface disease are realized in the preoperative evaluation and postoperative recovery from surgery, there are some intraoperative considerations as well. Any significant corneal surface irregularity, especially centrally, can affect the surgical view during cataract surgery. Similarly, heavy meibomian gland debris in the tear film from untreated posterior blepharitis can interfere with the surgical view or end up under the flap following LASIK surgery. An unhealthy corneal epithelial surface is more likely to be further damaged by multiple preoperative medications, dilating drops, intraoperative irrigation/manipulation, or applanation from cataract or refractive surgical femtosecond laser interfaces, thereby increasing the risk of intraoperative or perioperative epithelial defects.

While both cataract and refractive surgery can produce dry eye postoperatively,16 pre-existing disease can significantly increase the likelihood of symptomatic disease postoperatively. Postoperative dry eye can produce significant symptoms for our patients, which can be very difficult to treat. In addition, the ocular surface damage can produce significant discomfort as well as interfere with vision, producing significant light scattering, glare, halos, delays in visual recovery, and/or reduced best-corrected visual acuity. These effects may be particularly prominent in patients receiving a multifocal intraocular lens implant or a presbyopic corneal inlay. Identification and treatment of these conditions preoperatively allows a proactive approach, which can help to reduce the likelihood of these complications or allow better management should they occur. Identification of these conditions preoperatively also facilitates a conversation with the patient alerting them to the pre-existing condition prior to surgery, potentially avoiding a situation where the patient believes that the condition was caused by the surgery or a surgical complication.

HOW TO DIAGNOSE OCULAR SURFACE DISEASES PREOPERATIVELY

History

Ocular surface diseases, while common in surgical patients, are frequently overlooked by clinicians. In order to avoid the pitfalls described previously, it is important to have a high index of suspicion. Careful attention to the patient history is required. Complaints of dryness, itch, irritation, burning, grittiness, or foreign body sensation all suggest ocular surface diseases and should be taken seriously. If patients do not volunteer this information spontaneously, specific questions should be asked in order to determine whether they have experienced these symptoms. Validated instruments, such as the Ocular Surface Disease Index (OSDI)²¹ and Standard Patient Evaluation of Eye Dryness (SPEED) questionnaires²² are also helpful and may indicate functional difficulties associated with ocular surface disease. A patient history of fluctuating vision also suggests an unstable tear film. Fixed visual problems such as a cataract or refractive error tend to produce fixed visual problems or complaints. However, a fluctuating problem such as an unstable tear film will produce fluctuating vision, especially in the presence of another fixed deficit in the visual pathway, such as a cataract. A history of artificial tear use suggests that they are self-medicating their condition and strongly points to the presence of ocular surface disease. Many years of contact lens wear and/or contact lens intolerance also suggests the diagnosis. It is equally important to look at the patient’s list of systemic medications for those that may produce or worsen dry eye.

Point-of-Care Diagnostics

Once a careful history is taken, there are several point-of-care diagnostic tests that can be helpful indicators of the presence of dry eye. Many of these tests can easily be performed by technicians as part of their patient workup and are useful adjuncts to the workup of presurgical patients.

Osmolarity is a measurement of the concentration of dissolved solutes in a solution. In the tear film, the osmolarity is generally expressed in units of milliosmoles/liter (mOsm/L). Hyperosmolarity of the tear film is a recognized and validated marker of dry eye. Hyperosmolarity of the tear film occurs through decreased flow of the aqueous component of the tear film from the lacrimal gland, and/or through increased evaporation and instability of the tear film. Increased osmolarity of the tear film stimulates the release of inflammatory cytokines, enhances the rate of cell apoptosis, and results in a decrease in the number of goblet cells.23,24 Tear film osmolarity can be easily tested with a handheld device that is touched to the tear film and provides a digital readout of tear film osmolarity within seconds.

Patients with a normal tear film typically have a stable tear film osmolarity. A higher degree of fluctuation in tear film osmolarity is observed in patients with dry eye. Fluctuations occur both between measurements taken from the same eye and measurements concurrently taken between eyes of a patient. In general, an elevated tear film osmolarity is correlated with dry eye; the normal tear film osmolarity in patients without dry eye ranges from 270 to 308 mOsm/L (mean of 302 mOsm/L). A threshold of 308 mOsm/L has been found to be indicative of early/mild dry eye, while a tear film osmolarity of 316 mOsm/L or higher is correlated with moderate to severe dry eye. Based on the stability of the tear film in the eyes of normal patients, a difference in the tear film osmolarity of patients > 8 mOsm/L between eyes is indicative of dry eye disease.^25–27

The evaluation of osmolarity should be conducted prior to disturbance of the eye in order to obtain accurate results, as any disturbance to the ocular surface may stimulate reflex tearing, which can falsely lower the reading. While an elevated measurement of tear film osmolarity is a strong indicator for dry eye, the presence of an elevated osmolarity reading may not correlate with a patient’s symptoms or other clinical signs, due to the nature of the disease and fluctuations observed in these patients; trends observed through repeated osmolarity assessments are beneficial in the diagnosis of individual patients.^25,26

Matrix Metalloproteinase-9 Detectors

Recent research has evaluated matrix metalloproteinase-9 (MMP-9), an enzyme that is produced by corneal epithelial cells, as a biomarker for dry eye. The MMP family of enzymes plays an important role in wound healing and inflammation through the ability to degrade collagen. Elevated levels of MMP-9 have been observed in the tears of patients with dry eye.^26,27 The presence of MMP-9 over 40 ng/mL in the tear film has been correlated with the presence of the inflammatory component of dry eye disease. MMP-9 testing of the tear film can now be easily performed with a handheld disposable device that produces results within minutes. A positive test strongly suggests ocular surface disease–related inflammation on the ocular surface and should prompt the initiation of anti-inflammatory therapy.

Levels of several protein components of the lacrimal secretions have been found to be altered in the tear film of patients with ocular surface diseases, allowing these proteins to be used as biomarkers.28,29

Lactoferrin is one of the most abundant protein components of the healthy tear film. Lactoferrin, through the sequestration of iron, acts as an antimicrobial agent and plays a role in the immunological and anti-inflammatory properties of the tear film. The concentration of lactoferrin in the tear film has been observed to be reduced in patients with aqueous-deficient dry eye.³⁰ A point-of-care diagnostic for the measurement of the concentration of lactoferrin in the tear film of suspected dry eye patients is currently available. Lactoferrin levels below 0.9 mg/mL suggest the patient has aqueous-deficient dry eye, with the severity of the disease correlated with lower levels of the biomarker.^24,31

Immunoglobulin E (IgE) proteins, antibodies specific for particular allergens, are found in the tear film of patients with ocular allergic conditions. Exposure to allergen particles results in binding of IgE and interaction with mast cells in the conjunctiva, initiating the inflammatory response of the allergic cascade.^22,32

The same point-of-care test commercially available to measure tear film lactoferrin concentrations can also evaluate the level of IgE in tear samples. IgE levels ≥ 80 ng/mL suggest a diagnosis of allergic conjunctivitis, with the level of IgE present in the tear film correlating with the severity of the allergic condition.³³

Tear film IgE testing will also be available in the near future, coupled to the same device that currently performs MMP-9 analysis.

Meibomography

Meibomography, which is now readily available through the use of several devices, may also be a helpful adjunct in the diagnosis of meibomian gland disease. These noninvasive photographic devices visually display the meibomian gland architecture, revealing tortuosity, shortening or dropout—all of which are diagnostic of meibomian gland disease. The visual demonstration of the shortening or loss of meibomian glands is often very impactful and helps invest the patient in his or her diagnosis and treatment.

Tear Film Interferometry

The lipid layer of the tear film can also be directly visualized using interferometry, aiding in the diagnosis of evaporative dry eye, and allowing direct visualization of tear film stability. Colored images of the superficial layer of the tear film, the lipid layer, can be generated and evaluated to assess the thickness across the ocular surface.^31,34 A reduction in the thickness of the lipid layer (< 60 nm) has been correlated with meibomian gland dysfunction and symptoms of dry eye.

Conjunctival Impression Cytology

Conjunctival impression cytology, once reserved primarily for research centers, can now be performed easily in the office through the use of a new diagnostic device. While useful to demonstrate goblet cell loss and squamous metaplasia associated with dry eye, the results are not immediately available, unlike the other point-of-care diagnostics. A modification of this device to collect ocular surface disease biomarkers is also under development.

The height of the tear film meniscus should be inspected to evaluate the overall volume of tears on the ocular surface. Normal tear-film meniscus height is approximately 0.15 to 0.3 mm. Automated methods for evaluation of the tear film meniscus height and volume are now available and can be helpful. Fluorescein and lissamine green staining of the ocular surface are essential to evaluate tear film stability and to screen for ocular surface damage. Tear film breakup time is easily evaluated with a fluorescein stained tear film, and a breakup time of less than 10 seconds is considered abnormal.24 Automated tear film breakup time analysis is now also available. The fluorescein stained tear film may also reveal negative staining, in which subtle elevations on the ocular surface become evident as the fluorescein rolls off the high points and pools in the lower areas. This can be extremely helpful to reveal subtle ocular surface irregularities such as those seen with anterior basement membrane dystrophy, corneal degenerations, or scarring. Such irregularities can produce significant optical aberrations and can potentially have a profound effect on cataract and refractive surgery. It is important to be aware of these conditions preoperatively in order to properly counsel the patient and properly plan for the upcoming surgical procedure.

Ocular surface damage can be evaluated by looking at the fluorescein and lissamine green staining patterns. Ideally, there should be no staining. The presence of staining suggests the presence of ocular surface injury/damage from ocular surface disease. It is important to wait at least 2 minutes after instilling fluorescein or lissamine green prior to evaluating the staining patterns, as they can take time to develop; a casual, rushed examination may miss important diagnostic clues. Schirmer testing can also be useful in these patients, although it may not be routinely performed. Schirmer testing without anesthesia is particularly useful, because it demonstrates reflex tearing due to the irritation produced by the strips. If a patient only produces 5 mm or less of wetting after 5 minutes on this test, it strongly suggests the presence of dry eye.

Corneal topography is also an extremely useful tool to help diagnose ocular surface disease as well as corneal shape abnormalities and should be part of the workup of any patient undergoing ocular surgery. The incidence of keratoconus in the general population is approximately 1/2000,35 although there are many more individuals with undiagnosed, mild, or forme fruste disease. Those patients often present for refractive surgery evaluation, and corneal topography and/or tomography is essential to help identify those patients who would otherwise be at high risk for ectasia postoperatively. Similarly, patients with mild disease may present for cataract surgery later in life, having never been diagnosed with the condition. Corneal topography can reveal the characteristic pattern, which would have otherwise gone unrecognized, thereby providing essential information for the patient and the clinician. The patient can now be counseled as to the presence of the condition, and the surgeon can make better choices regarding intraocular lens selection. The use of a multifocal lens in these patients is generally contraindicated, and the refractive response to toric lenses may be unpredictable.

Previously unrecognized corneal irregularities can also be diagnosed with corneal topography. A pattern of irregular astigmatism may be seen in corneal dystrophies, such as anterior basement membrane dystrophy, and stromal dystrophies, such as granular, lattice, or Avellino dystrophy. While the stromal dystrophies tend to be easily observable on slit-lamp evaluation, basement membrane dystrophy can be extremely subtle and easy to miss. Map-dot-fingerprint basement membrane changes are common, affecting up to 76% of the population over age 50 years and between 6% and 42% of the general population,^36,37 and can produce subtle irregular astigmatism that can affect vision. Subtle grayish “maps” or fine fingerprint lines can be seen under the slit lamp with careful observation. However, often these findings are missed. Instillation of fluorescein in the tear film often reveals negative staining indicative of the underlying condition and underscoring the surface irregularity. Corneal topography can similarly reveal the irregular pattern, and the finding of irregular astigmatism without a known cause should prompt a second look at the ocular surface to rule out abnormalities.

Corneal topography is also an excellent screening tool for unstable tear film and ocular surface disease. Since Placido-based corneal topography depends on analysis of reflected rings projected onto the ocular surface, irregularities of the tear film or ocular surface will distort those rings, producing areas of uninterpretable data. These areas with no interpretable data are graphically represented on the color printout as white spots within the color map (Figure 4-1). These white spots of missing data may be considered similar to dry spots on the ocular surface and should raise the suspicion of ocular surface disease. The presence of these white spots should prompt a second look at the patient and a thorough evaluation for the presence of ocular surface disease.

The presence of irregular astigmatism on corneal topography is another diagnostic clue, not only suggesting the possibility of a corneal shape abnormality as discussed previously, but also potentially indicating an unstable tear film. The irregular tear film with a rapid breakup time distorts the reflected corneal rings producing a computer interpretation of an irregular shape. This irregular shape is graphically represented by an asymmetrical distribution of color on the corneal topography printout (Figure 4-2). The presence of these topographic irregularities without a previously known cause of irregular astigmatism should prompt a second look at the cornea to rule out a structural cause, such as anterior basement membrane dystrophy, as mentioned previously. In the absence of any structural cause of irregular astigmatism, an unstable tear film due to the presence of ocular surface disease must be considered.

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