Cataract Surgery in Uveitic Eyes

Strategies for success in this challenging patient population.

By Michael Saidel, MD

Cataract surgery in uveitis represents one of the most difficult challenges for anterior segment surgeons. With proper preparation, however, the ophthalmologist can perform successful surgery and achieve good outcomes. A thoughtful approach toward preoperative planning, intraoperative technique and postoperative management will be most successful.

Background

Uveitic cataracts develop for a variety of reasons. In flammation itself can lead to a breakdown of the blood-ocular barrier. Plasma phospholipids (e.g., lysophaphatidylcholine, phasphatidylcholine) may enter into the eye, leading to an increase in lens epithelial permeability.^1,2 Phospholipase A activity may also play a role.^3,4 Frequently, uveitic cataracts have an iatrogenic component. Steroids are the most common culprits. Steroids cause cataracts by several mechanisms.⁵ They inhibit the sodium/potassium/ATPase pump. Steroids also bind to lens proteins, leading to lysine-ketocorticosteroid formations. Oxidation of sulfhydral protein groups may also lead to cataract formation. Additionally, systemic conditions and medications such as steroid-induced glucose intolerance may lead to cataract formation.⁶ Less commonly, cholinergic agents used for treatment of glaucoma may play a role.

Preoperative Considerations

While knowing the cause of the uveitis may help guide therapy and predict outcomes, establishing the diagnosis is frequently impossible. Most ophthalmologists are able to establish a diagnosis in roughly half of their cases, although some tertiary centers report higher numbers.⁷ The surgeon should obtain appropriate medical history and labs. Using descriptive categories may help map the postoperative outcome, even when the etiology remains uncertain.

For example, a 55-year-old African-American woman with bilateral, diffuse uveitis and retinal perivasculitis suggests a different outcome than the 55-year-old Caucasian male with unilateral, anterior uveitis, stellate keratic precipitates and heterochromia. In the case of the former, even without a tissue diagnosis, one may predict an outcome similar to those seen in sarcoidosis (such a scenario is common in presumed sarcoidosis limited to the eyes), whereas the latter case suggests Fuchs’ heterochromic iridocyclitis (FHI). While both cases may remain idiopathic, the description may help guide the surgeon.

Patient Assessment

Patient selection is key in all cataract surgery. While the visually significant cataract remains the chief reason for surgery, the uveitic patient has unique considerations. Perhaps the surgeon will choose to undertake surgery because there is a poor view of the fundus for examination or therapeutic pars plana vitrectomy. Perhaps the patient has phacoantigenic uveitis. All uveitics need to be counseled about the risks of decompensation. Unlike most cataract patients, uveitics are at risk for profound postoperative inflammation that in the worst-case scenario can require additional surgery or lead to profound visual loss and blindness.

Timing the Surgery

The timing of cataract surgery in the uveitic is probably the single most important factor and is strongly influenced by both patient and surgeon impatience. It is crucial that the patient achieve at least three months of quiescence prior to surgery.^8,9 The terminology more commonly used in the chronic disease literature is “durable remission.” It is important for the surgeon to consider this prior to engaging in the procedure. If it is at all possible, the patient should be in a steroid-free durable remission for three months. This means that the patient has no cells in their anterior chamber during this time.

Is such a “zero-tolerance” policy for three months achievable in all cases? White blood cells in the anterior chamber represent inflammation. Anterior chamber flare, however, may be a different issue. Because flare is caused by leakage of protein into the aqueous, breakdown of the blood aqueous barrier from chronic inflammation may lead to a flare that does not respond to therapy. Indeed, the patient may have no evidence of cell whatsoever and be in a durable remission of their uveitis but have recalcitrant flare. In this case of flare without cell, the surgeon should consider the anterior chamber free of inflammation. Nevertheless, because of breakdown of the blood-ocular barrier, anterior chamber activity may not be able to be eliminated. Such prior damage of the blood-ocular barrier may affect visual outcome.¹⁰

Figure 1. Most uveitis cases will benefit from immunosuppression prior to surgery. In cases such as this one of phacoantigenic uveitis, it is best to quiet the eye as much as possible before cataract extraction.

Concomitant Disease Issues

Comorbid factors need to be part of preoperative considerations. Glaucoma is frequently associated with uveitis, and cataract surgery can cause failure of a filtering bleb. When possible, cataract surgery should be done first.

Diabetes, whether iatrogenic from systemic corticosteroids or not, is a relatively common consideration in uveitis cataract surgery. Because the ophthalmologist will frequently be using systemic prednisone, the primary care physician will need to be notified in these patients. Typically, the insulin-dependent diabetic is easier to manage because patients can increase their insulin to compensate for corticosteroid-induced hyperglycemia. Non-insulin diabetics are paradoxically harder to manage, so guidance from the primary care physician is encouraged. Ophthalmologists are accustomed to easy preoperative courses; this is one case where one must be careful and take time.

Intraocular comorbid factors will play a major role in the final visual acuity. By far, the most common issue is cystoid macular edema. CME must be addressed and managed prior to surgery whenever possible. Additionally, depending on the etiology of the uveitis, the patient may have issues such as optic atrophy, vitreous/pars plana inflammation or retinal vasculitis. Thus, any intermediate or posterior uveitis must also be quiescent, requiring the help of a retina specialist.

The Value of Immunosuppresion

Preoperative immunosuppression is key in achieving a good outcome. The type of uveitis determines the type of immunosuppression. If the patient is in a durable remission off of therapy, it is reasonable to use the agent that induced remission initially. (Most of the therapies discussed herein are off label). For example, if the patient has Vogt-Koyanagi-Harada Syndrome managed with methotrexate, it would be reasonable to continue this therapy and add additional therapy perioperatively. Consider enlisting the aid of the patient's rheumatologist in such a case. While this choice is very much the decision of the surgeon and must be tailored to the patient, a few guidelines are helpful:

► Use of topical steroids such as prednisolone acetate 1% six to eight times daily starting one week before surgery or difluprednate emulsion 0.05% (Durezol, Alcon) four times daily starting one week before surgery.

► Systemic steroids are extremely useful in the perioperative period and are strongly encouraged. Prednisone is given 1-2 mg/kg starting two-to-seven days prior to surgery, planning for a taper over approximately one month after surgery. When using systemic steroids, the physician may want to consider protecting the patient from bone loss. Use of a calcium/vitamin D supplements such as OsCal (GlaxoSmithKline) 500 mg/200 IU PO BID can be helpful. Gastrointestinal prophylaxis with a histamine 2 blocker or proton pump inhibitor should also be considered.

Topical NSAIDs are commonly used in non-uveitic cataract surgery and should be considered in any uveitis case. Systemic NSAIDs such as celecoxib (Celebrex, Pfizer) are also useful. Special care should be taken to protect the gastrointestinal lining when mixing NSAIDs and steroids.

Sub-Tenon's, trans-septal and intravitreal steroids are very useful in maintaining quiescence before and after surgery. Use of long-lasting steroids such as depot triamcinolone should only be used if the patient has proven to not be a steroid responder or if the surgeon is prepared to manage steroid-induced glaucoma.

Additional Evaluations

In order to obtain good keratometry and biometry for lens selection, band keratopathy must be managed. After calcium removal, the cornea should be allowed to heal to get optimum readings. Band keratopathy can be debrided and chelated with disodium EDTA. (Importantly, use disodium—not calcium—EDTA.) Avoid violating Bowman's layer and use a bandage soft contact lens until re-epithelialized.

As mentioned above, the type of uveitis may predict the postoperative course. Different causes of uveitis predispose the patient to various complications such as glaucoma, posterior capsule opacity, hyphema, corneal edema, vitritis and CME. For the cataract surgeon, evaluating for such posterior segment imaging with fluorescein angiography or OCT will help identify problem cases. B-scan ultrasonography is necessary in cases of poor view to the retina.

Appropriate adjunctive measures can be taken for different types of uveitis. For example, in the patient with herpes simplex uveitis, systemic antivirals such as acyclovir or valacyclovir can be used. In toxoplasmosis, consider prophylactic antiparasitic drugs in patients at risk from a nerve or macula-threatening lesion.¹¹ The incidence of cataract in patients with Fuchs’ heterochromic iridocyclitis is high. While the canon suggests postoperative inflammation is low in FHI, the risk may be much greater.^12,13 Using appropriate care to prevent postoperative inflammation in FHI will serve patients well. In Behcet's disease, preoperative inflammation in the year prior to surgery predicts postoperative development of inflammation.¹⁴

Ultimately, preoperative planning will best predict the outcome of cataract surgery in uveitis. By obtaining a durable remission for three months prior to surgery, by managing comorbid factors, and with preoperative immunosuppression, the best outcomes will be achieved.

Intraoperative Considerations

Surgeons concentrate on operative issues in uveitis patients. It cannot be overstated that preoperative control of inflammation is the best predictor of good outcomes. Many surgeons will use intraoperative intravenous steroids such as methylprednisolone to aid in this process.

Management of the pupil represents the most common intraoperative concern. The surgeon must be prepared to perform a variety of maneuvers to handle this issue. A few techniques short of inserting a device should be initially employed. Viscomydriasis and synechialysis may be required. When breaking synechia, it is suggested that the surgeon perform this gently in order to avoid ripping the iris. Posterior synechia can form from pupil margin to iris root, so synechiolysis should be performed out into the periphery. An additional paracentesis may be required to provide access.

If the pupil refuses to dilate because of pupillary membrane, the intraocular scissors and forceps can be used to gently peel the membrane, taking care to minimally damage the iris.

Figure 2. Achieving a durable remission of at least three months prior to surgery will diminish the likelihood of postoperative inflammation such as this.

Expanding the Pupil

If the pupil refuses to dilate after these procedures, a variety of iris hooks and pupil expanders are available on the market. The author prefers simple iris hooks. With minimal experience, they can be placed in less than two minutes.

A few pearls to quick and easy insertion:

► Make all the incisions for the hooks first.
► Place the incisions posteriorly to avoid tenting the iris with the hooks.
► Point the knife toward the edge of the pupil so that the hook will point to grab the iris margin easier.
► Then set all of the hooks on the cornea. Viscoelastic on the cornea can be useful to keep the hooks in place.
► Without trying to get the hooks onto the iris, place all of the hooks (use four or five) into the pre-made incisions. Then, one-by-one, attach the hooks to the iris margin without making much effort to expand the pupil.
► Once the hooks have been attached, go back through to widen the pupil carefully to avoid ripping the iris. The iris does not need to be stretched to a huge diameter. Simply open it to the size you require for a safe rhexis. Use of a smaller aperture will reduce iris trauma.

Other iris expanders are useful and should be tried. The Malyugin ring (MicroSurgical Technology) comes in 6.25- and 7.0-mm sizes. The PerfectPupil (Milvella), marketed for intraoperative floppy iris syndrome, is effective in expanding small pupils. A similar device is the Morcher Pupil Dilator (Morcher GmbH). The Graether Pupil Expander (Eagle Vision) can be inserted with one hand and is silicone.

Continuing the Surgery

Once the pupil has been expanded, capsular staining is performed when necessary by injecting BSS under the viscoelastic followed by dye. Of course, the surgeon can use his or her preferred technique, knowing that if they prefer to use air, viscoelastic inserted previously will have to be dealt with appropriately.

Elastic and fibrotic anterior capsules are a common problem in uveitis. The surgeon may employ the can-opener cap-sulotomy. By placing the nicks in the anterior capsule very close to each other, especially in the young patient with an elastic capsule, the capsulotomy can approach a curvilinear capsulorhexis. When a plaque is present, by gently pushing and pulling on the plaque, an opening can be made around it. Occasionally, intraocular scissors or the vitrector are required. A pearl here is that if the anterior capsule is abnormal, expect nothing less from the posterior capsule.

Because many uveitic cataracts are limited to posterior subcapsular and may be very soft, the surgeon must be comfortable with phacoaspiration. For the rock-hard nuclei, consider using chop techniques and liberal use of viscoelastic such as the soft shell technique.

Uveitis patients frequently have compromised zonules. This may be due to chronic inflammation or trauma. Prior intraocular surgery (AC taps, iridectomy, trabeculectomy, vitrectomy) may cause weakened zonules. Use of the capsular tension ring in such cases may be appropriate.

Lens Selection and Placement

The use and placement of intraocular lenses in uveitis has been controversial in the past. Nevertheless, hydrophobic acrylic lenses are generally well tolerated.

It has been shown that polypropylene haptics activate complement. First-generation silicone lenses were shown to exacerbate uveitis. If the patient might need silicone oil (for retinal detachment or management of hypotony), avoid using a silicone IOL. Intracapsular fixation is always preferred, but uveitic eyes can do well with sulcus fixation. Avoid using a single-piece, sharp-edged lens in the ciliary sulcus. If a secondary IOL is to be placed, slceral fixation is preferred over iris fixation. Because some patients can form a fibrin “cocoon” around IOLs, be prepared to remove a lens when necessary.

Intraoperatively, devices can be placed into the posterior segment. The Retisert and Ozurdex implants are both FDA-approved for management of posterior uveitis. Retisert (fluocinolone acetonide, Bausch + Lomb) lasts for approximately 30 months. Ozurdex (dexamethasone, Allergan) is injectible, lasting approximately 1-3 months.

Postoperative Considerations

After the surgery, if retrobulbar or peribulbar anesthesia was given, keep the patch and shield on overnight. There is no need for patients to instill drops if they were given appropriate immunosuppresion and antibiotics. If pressure is an issue, consider using acetazolamide or methazolamide by mouth. Acetaminophen is used for pain. Topical cases can start taking their drops immediately.

On postoperative day one, remove the patch and shield. Perform the typical post-operative exam including vision, pressure, check wounds, level of inflammation, lens placement and a view of the fundus.

Discuss the medical regimen with the patient in detail. Continue the systemic meds that induced remission of the uveitis. For PO steroids, use approximately 1 mg/kg of prednisone for one week, then taper, varying based on the level of inflammation. This is usually reducing the dose of prednisone by 10 mg every week over a four-to-six week period. For topical steroids, use either prednisolone acetate 1% every hour (shake vigorously) or difluprednate emulsion 0.05% four times daily. Use your typical antibiotic regimen. Topical homatropine 5% BID is useful in reducing the risk of posterior synechia. Use topical NSAIDs as before surgery.

Typically, we see the patient on days 1, 7 and 21, tailored to the needs of the patient with extra visits required for inflammation and IOP issues. After the first month, the patient is seen regularly as appropriate.

Postoperative Complications

Despite best preoperative efforts, some patients have excessive postoperative inflammation. Again, the surgeon must remember that the key to avoiding this problem is prevention. Make every effort to achieve three months without inflammation preoperatively, ideally without steroids, then add steroids perioperatively and the agent that induced remission to ensure continued quiescence.

For persistent inflammation (3+ or more cells in the anterior chamber at two weeks), use steroids by mouth, intraocular or periocular. In cases with steroid-induced glaucoma, peri- or intraocular methotrexate can be used.

If the patient is unable to be tapered below 10 mg of prednisone by mouth, consider investigating. Is it possible the patient has endophthalmitis? Does the patient require a tap and inject? Does the patient require a PCR? Is the IOL in the correct position? Could the IOL be rubbing on the iris?

Dealing with CME

CME is the bane of the cataract surgeon. Attempting to treat CME in the context of inflammation is futile. With this in mind, treatment of inflammation will be the first goal. In a quiet eye, standard CME treatments are appropriate, including NSAIDs (topical and PO), periocular steroid injections, carbonic anhydrase inhibitors (topical and PO). With the advent of anti-VEGF agents, we have a new mode of treating CME. Certainly, other medical treatment options will appear, but for now vitrectomy with membrane peel is a good surgical therapy for CME.

Treating PCO and Fibrin Deposits

Posterior capsular opacification and fibrin deposits on intraocular lenses are more common in uveitis. When deciding to treat PCO, consider if the opacity warrants a laser procedure, based on patient visual acuity or function. As with cataract removal, it is advised to wait until inflammation is controlled. Use aggressive topical steroids after laser capsulotomy. We have had mixed results using tissue plasminogen activator for dissolving fibrin clots.

Glaucoma

Glaucoma is commonly associated with uveitis for a variety of reasons. Aggressive use of topical and/or oral pressurelowering agents is warranted. The concern of prostaglandin analogs inciting inflammation does not seem to be warranted for these agents.¹⁵ Laser peripheral iridotomy is effective in uveitis especially for light-colored irises and controlled inflammation. For darker irises, a surgical PI may be necessary. In any case, aggressive use of steroids is appropriate. Topical and periocular steroids will more commonly cause IOP spikes than systemic steroids, although oral steroids can cause a steroid response as well. In the case of uncontrolled glaucoma, the ophthalmologist can turn to either laser or surgery, depending on the needs of the patient and the level of inflammation.

Conclusion

With planning and a special focus on perioperative immunosuppression, the ophthalmologist can expect good outcomes in cataract surgery in uveitis. A durable remission of three months prior to surgery and the use of the agent that induced remission in the perioperatvie period are the best bet for a smooth postoperative course. While the intraoperative architecture may provide some challenges, they are well within the skills of the anterior segment surgeon. Postoperatively, CME must be treated when it arises. Treating CME in the setting of inflammation is futile, so inflammation must be controlled from three months prior to surgery into the postoperative period. OM

References

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