Perioperative Management of Uveitic Cataracts

SYNOPSIS

Uveitis patients represent a unique subset of the population undergoing cataract surgery and pose several challenges that require special consideration and strategy. Maintenance of disease quiescence for at least three months prior to surgery maximizes postoperative outcomes, though these patients remain at increased risk for pseudophakic cystoid macular edema, which can be refractory to the traditional steroid treatments. In this review, we detail the pillars of preoperative optimization, intraoperative considerations, and postoperative management of uveitic cataracts, with special attention on the evidence surrounding prevention and treatment of refractory postoperative cystoid macular edema.

Introduction

Cataracts commonly develop in patients with uveitis as a result of chronic inflammation and longterm steroid use. While postoperative prognosis is significantly improved in these patients with the development of more potent anti-inflammatory drugs and advances in microsurgical techniques, uveitis patients remain at increased risk for postoperative complications, including persistent postoperative inflammation and cystoid macular edema. No standardized guidelines remain regarding prophylaxis against, and management of, cystoid macular edema following phacoemulsification in these patients. The purpose of this review is to describe evidence from the literature regarding cataract surgery and lens implantaation in patients with uveitis, with special emphasis upon the evidence surrounding prevention and management of refractory cystoid macular edema.

Significance

PREOPERATIVE OPTIMIZATION

Thorough patient evaluation is paramount to selecting appropriate candidates for surgery, counseling patients of potential outcomes, and anticipating operative challenges. Characteristics of patients and their uveitis can predict surgical and visual outcomes; individuals prone to more inflammation, such as younger patients and those with disease entities that affect the posterior segment, tend to do poorer. Overall, eyes affected by acute as opposed to chronic uveitis do better, and eyes with anterior uveitis have the best outcomes.¹ Patients with Fuchs heterochromic iridocyclitis have been found to have better prognosis than those with juvenile idiopathic arthritis and other types of anterior uveitis, though they also are at increased risk of intraocular pressure (IOP) elevation following cataract surgery.¹ Amongst those with posterior or panuveitis, patients with Behçet’s disease, Vogt-Koyanagi-Harada syndrome, and sympathetic ophthalmia tend to have inferior visual outcomes due to preexisting ocular pathology, including optic atrophy and retinal ischemia, atrophy, and scarring.^2,3 Of note, this does not necessarily preclude these patients from visual improvement after cataract surgery. The Multicenter Uveitis Steroid Treatment (MUST) Trial found that patients with noninfectious intermediate, posterior, and panuveitis who underwent cataract surgery experienced improvement in visual acuity of about 23 letters that was sustained over nine months of followup.⁴ However, these patients still remain more likely to develop postoperative inflammation and cystoid macular edema (CME), the major vision-limiting complication following cataract surgery in uveitis patients. In their cohort, the UK Pseudophakic Macular Edema Study Group reported a greater proportion of uveitic patients have small pupils, require additional surgical procedures, suffer more intraoperative complications, and have poorer postoperative visual outcomes, often due to their increased risk of CME.^5,6 Patients with preexisting, sight-limiting pathology should be advised of the reduced prognosis for visual improvement, with a detailed discussion of the risks, benefits, and expectations for surgery. Finally, once the decision has been made to proceed with surgery, identifying comorbidities are of utmost importance for planning one’s surgical approach. Many pre-existing uveitic sequelae, including band keratopathy, miotic pupils, iris atrophy, posterior synechiae, and pupillary membranes, can complicate cataract extraction in these patients, and, therefore, it is crucial to perform a careful pre-operative exam at the slit lamp to detect and prepare for these anatomic challenges.

Control of inflammation is vital to improving surgical and visual outcomes (Figure 1). At this time, the standard recommendation is to maintain at least three months of quiescence prior to cataract surgery, which may necessitate the use of immunomodulatory therapy for control of inflammation. Several studies have demonstrated that patients who are quiescent for at least three months have comparable outcomes to the standard population undergoing phacoemulsification, while those with active inflammation within three months of surgery have greater risk of intraoperative and postoperative complications, as well as development of post-operative CME.⁷ Current prophylactic inflammation control measures have overall been successful in preventing recurrence. In a longitudinal study out of Moorfields, 309 eyes with uveitis that underwent the prophylactic inflammation control measures (perioperative systemic prednisolone or intravitreal triamcinolone) had no significant increase in relapse of uveitis, or change in topical or systemic steroid dosing following surgery compared to the pre-surgery period.⁸ Uveitic eyes treated with perioperative oral corticosteroids have been found to have a seven-fold reduction in postoperative CME.⁷ For the uveitic population, it is common to consider preoperative inflammation prophylaxis with oral steroids dosed at 1 mg/kg/day for up to one week prior to surgery. Periocular or intraocular steroids in the form of triamcinolone or dexamethasone implants have been utilized for prevention of inflammation. Intensive topical steroids (six to eight times per day) or intravenous methylprednisolone may serve as an adjunct or alternative to oral steroids. Mora et al. performed a comparison of frequent topical steroids versus the same topical regimen combined with oral steroids for perioperative prophylaxis in patients with non-infectious uveitis, finding comparable outcomes in terms of improvement in visual acuity, intraocular pressure variation, central macular thickness, and uveitis relapse.⁹ A single dose of 15 mg/kg intravenous methylprednisolone 30 minutes before surgery has been shown to be equivalent to a two-week course of oral prednisolone 0.5 mg/kg in terms of visual acuity outcomes and rates of CME at seven and 90 days after surgery.¹⁰

Figure 1.

Perioperative management considerations for uveitic cataracts

Though this review focuses on the management of non-infectious uveitides, it is important to mention that for infectious uveitides, one should consider prophylaxis with antimicrobials to prevent reactivation after surgery. For herpetic uveitis cases, one should consider antiviral prophylaxis with oral acyclovir 400 mg twice daily or valacyclovir 0.5 g daily preoperatively and for 2-3 weeks postoperatively. Topical NSAIDs are associated with less risk for herpetic corneal recurrence than topical steroids, and thus may be used concurrently to lower the dose of topical steroid required in the postoperative period.¹¹

INTRAOPERATIVE CONSIDERATIONS

Intraocular lens placement and material selection

Traditionally, intraocular lens (IOL) placement at the time of cataract extraction has been deferred for those at high risk for postoperative inflammation, such as patients with intermediate uveitis and juvenile idiopathic arthritis, with secondary IOL implantation considered in the future if inflammation is well controlled. However, a recent meta-analysis of 89 articles revealed that more eyes that received intraocular lens implantation at the time of surgery achieved vision 20/40 or better than those that were left aphakic (71% versus 52%).² This may be confounded, though, by the general trend towards deferring IOL implantation in patients with poorly controlled disease, who are at more risk for underlying vision-limiting pathology.

As with standard cases, IOL placement in the capsular bag is ideal, but if unable to be done safely, the IOL may also be placed in the sulcus or fixated to the sclera.¹¹ Given the increased risk of inducing inflammation, anterior chamber IOLs should be avoided in uveitic patients. Among the available lenses, implantation of acrylic and heparin-surface-modified polymethylmethacrylate (HSM PMMA) IOLs are associated with better visual outcomes and less recurrent inflammation than non-HSM PMMA and silicone IOLs.^2,3 A Cochrane review in 2014 reported the results of four randomized controlled trials, in which fewer eyes with hydrophobic acrylic IOLs developed posterior synechiae than eyes with silicone IOLs, but there were no significant differences found in risk of posterior capsule opacification (PCO), corneal edema, CME, or IOL decentration.¹² Silicone IOLs should generally be avoided as uveitic patients are at risk for posterior complications requiring future vitreoretinal procedures, including silicone oil placement.

Surgical planning

Several special techniques may be needed to successfully accomplish cataract extraction in uveitic patients. Often, one performs synechiolysis for posterior synechiae, and retracts the iris using ophthalmic viscoelastic devices, iris hooks, and pupil expanders for miotic pupils.¹¹ Trypan blue can aid visualization during capsulorrhexis in white cataracts. In terms of surgical approach to lens removal, phacoemulsification and nuclear expression cataract extraction have been found to achieve similar visual outcomes.² For patients with chronic uveitis with posterior segment pathology, such as cystoid macular edema, vitreous opacities, or retinal or choroidal neovascularization, one may consider combined cataract extraction with vitrectomy, which has been associated with more rapid visual recovery, though the data on the outcomes of this approach generally remain limited.^{13, 14}

The addition of intraoperative steroids to the preoperative regimen has become instrumental for quelling excess inflammation after surgery in this population. Patients on chronic steroids should receive a stress dose on the day of surgery, either in the form of a 500 to 1000 mg bolus of intravenous methylprednisolone at the time of surgery or intravenous dexamethasone.^14,15 Injection of intracameral or intravitreal triamcinolone or surgical implantation of a fluocinolone acetonide implant can further decrease postoperative inflammation and fibrin formation in the anterior chamber, though these carry a significant risk of intraocular pressure elevation.¹⁴

POSTOPERATIVE COMPLICATIONS AND MANAGEMENT

Cystoid macular edema

One of the most common sight-limiting complications of cataract extraction is cystoid macular edema (CME). Patient with uveitis are known to possess an increased susceptibility to developing pseudophakic CME, with the greatest risk in those affected by intermediate, posterior, or panuveitis; those who have suffered recurrent CME during flares; and those who have recurrent uveitis within three months of surgery.^3,6 The underlying mechanism is thought to be related to breakdown of the blood-ocular barrier secondary to surgical manipulation and postoperative inflammation, after which transudate accumulates within the retina with subsequent clinically significant edema.¹⁶

Typically, patients are placed on a postoperative regimen of topical non-steroidal anti-inflammatory drugs (NSAIDs) and steroids to attenuate postoperative inflammation and risk of CME (Figure 2). A meta-analysis examining 16 RCTs with a total of 2898 eyes undergoing prophylaxis with topical NSAIDs or steroids revealed a decreased incidence of angiographic and clinically relevant CME, as well as improvement in vision versus controls.¹⁷ The addition of topical NSAIDs to steroids has been shown to significantly reduce central foveal thickness and pseudophakic macular edema in high-risk eyes, including those with uveitis.¹⁸

Figure 2.

A. Pseudophakic cystoid macular edema and recurrent uveitis following cataract surgery in a patient with history of sarcoidosis. B. Resolution of CME with topical corticosteroids (difluprednate) and NSAID (ketorolac) therapy.

Should there be CME refractory to topical agents, one typically escalates to local subconjunctival, posterior sub-Tenon, or intravitreal steroid injections, which are more potent than topical therapy and avoid the adverse effects of systemic steroids, such as hyperglycemia and hypertension. A comparative study among subconjunctival, sub-Tenon’s, and intravitreal steroids found that there were no significant differences in visual acuity improvement, central macular thickness, or tolerability among the treatments.¹⁹ However, another study suggested that intravitreal delivery of triamcinolone is superior to orbital floor injections for macular edema, inflammation, and visual outcome after cataract surgery in uveitis patients.²⁰ Intravitreal triamcinolone (IVTA) has consistently shown efficacy in uveitic macular edema, as well as patients with posterior uveitis who experience pseudophakic CME.^21-23 In a study out of Moorfields, 19 eyes with posterior uveitis that did not undergo systemic corticosteroid prophylaxis before cataract surgery due to underlying conditions that were at risk for exacerbation (diabetes and hypertension) were given IVTA at the time of surgery.²¹ No patients experienced a decrease in visual acuity, with 17 out of 19 achieving visual acuity of 20/40 or better; the remaining two were limited by optic atrophy and macular edema. Also no development of macular edema occurred within four months of surgery. Elevated IOP occurred in three out of 19 patients, but was controlled medically and resolved after three months. This suggests that IVTA could be a good alternative to systemic steroids for prophylaxis against postoperative CME, though the study sample is small and only provides data for short-term follow-up.

Longer-acting steroid implants, including the intravitreal, sustained-release dexamethasone implant (Ozurdex) and surgically implanted fluocinolone acetonide implant (Retisert), also are utilized for refractory uveitic and pseudophakic macular edema, and have demonstrated efficacy as a preventative measure against the occurrence of macular edema and recurrence of uveitis in the perioperative setting.^24-26 Williams et al. reported results of a randomized controlled trial of 41 patients with persistent macular edema from uveitis or post-cataract surgery who were randomized to one of two dosages of dexamethasone (350 or 700 micrograms) or observation; those who received the 700-microgram dexamethasone implant had the most significant improvement in VA and fluorescein leakage.²⁷ Observed improvement in VA and central retinal thickness appears to last for up to twelve months following implantation of dexamethasone, and these effects may be comparable or even superior to those achieved by systemic immunosuppression.²⁶ These implants may be administered either prior to or at the time of cataract surgery with benefits seen regardless of timing, though possibly to a greater degree when implanted closer to the time of surgery. Larochelle et al. found a decrease in central macular thickness in patients who received the intravitreal dexamethasone implant and underwent phacoemulsification within four months of implantation. Those who underwent surgery within four weeks of dexamethasone implantation experienced a greater decrease in macular thickness versus those who had surgery greater than four weeks later.²⁸ In terms of the fluocinolone acetonide implant, the MUST Trial examined 148 eyes with uveitic macular edema randomized to Retisert or systemic immunosuppression; about two thirds of both groups experienced improvement or resolution of macular edema, but the implant group was noted to have more quantitative improvement in retinal thickness.²⁹ Another study by Chieh et al. evaluated 24 eyes with severe intermediate, posterior, or panuveitis requiring immunomodulatory therapy, periocular corticosteroid injections, or both who underwent phacoemulsification with IOL implantation and fluocinolone acetonide implant insertion during a single surgical session. These patients experienced improvements in visual acuity and central retinal thickness, as well as a decrease in uveitis recurrences and need for topical and periocular steroids and systemic immunosuppression.³⁰ While it appears that these implants have good efficacy for refractory disease and may improve outcomes following phacoemulsification, they also carry a significant risk of long-term intraocular pressure elevation. One must take into account the status of the patient’s optic nerve and presence of glaucoma prior to consideration of these implants, especially as further and persistent elevation of intraocular pressure may necessitate eventual glaucoma filtering surgery.³⁰

Lower-dose intravitreal fluocinolone acetonide implants, including Iluvien and Yutiq, have recently been developed for use in noninfectious uveitis. Unlike Retisert, they can be administered in-office, and incur less risk of cataract formation and glaucoma. A single case report in the literature from 2016 describes results of Iluvien implantation in a patient with intermediate versus panuveitis who suffered intractable inflammation and macular edema of the left eye despite aggressive topical difluprednate and a history of bilateral Retisert insertion.³¹ Improvement in visual acuity and macular thickness occurred within three weeks of Iluvien implantation and was sustained through eight months of follow-up, without rise in IOP or recurrence of active inflammation. Though further comparative studies are needed to elucidate these newer implants’ relative impact on macular edema, they represent potential alternatives to Retisert with advantages of ease of administration and fewer adverse effects.

Finally, systemic therapy with oral and intravenous steroids have shown to decrease the incidence of perioperative CME, and generally are recommended prior to surgery for patients with a history of severe inflammation, as well as monocular patients who lost their fellow eye to inflammation. A typical regimen of oral prednisone consists of 0.5 mg/kg starting three days before surgery, with a taper of 5 mg each week until a dose of 10-20 mg daily is reached, after which a more gradual taper of 2.5 mg each week is followed until patients reach pre-surgery dosing or the lowest required maintenance dose. Eyes treated with perioperative oral steroids have demonstrated a seven-fold reduction in postoperative CME at one and three months after surgery.⁷ It remains unclear whether local or systemic therapy is superior for CME. In a head-to-head study of 40 patients who received either intraoperative IVTA or postoperative oral steroids, postoperative CME was seen in three out of 20 patients in the steroid group as opposed to one out of 20 patients in the IVTA group, with lower central foveal thickness and more resolution of angiographic CME in the triamcinolone group.³² On the other hand, a comparison between intravitreal dexamethasone implant and postoperative oral steroids in 20 patients with uveitis who underwent phacoemulsification with IOL implantation found no significant difference in central macular thickness or IOP.³³ For patients who do not respond to oral steroids, a short course of intravenous pulse methylprednisolone may be indicated. Small studies of refractory pseudophakic and uveitic CME have shown improvement or resolution of disease within three days of IV methylprednisolone followed by a rapid oral taper, without a significant rise in IOP.^34,35

Posterior capsule opacification

Posterior capsule opacification remains the most common late complication of cataract surgery among patients with or without uveitis. Strategies discussed in the preoperative optimization section, including deferring surgery until inflammation is controlled for at least three months, and implantation of acrylic IOLs may decrease the risk of PCO, though overall the rates remain high at about 18% at ten years despite these measures.^3,6,36 Generally, it is recommended that one should wait until inflammation is controlled before attempting Nd:YAG capsulotomy.

Intraocular pressure

Uveitis patients are vulnerable to fluctuations in intraocular pressure. Hypotony may result from persistent inflammation and require increasing topical and systemic anti-inflammatory therapy, particularly steroids that additionally serve to maintain intraocular pressure. On the other hand, persistent elevation of intraocular pressure may occur secondary to steroid response, in which case one may need to taper topical steroids and increase oral and/or systemic immunosuppression for persistent inflammation. Of note, patients with Fuchs heterochromic iridocyclitis may specifically be at increased risk of intraocular pressure elevation following cataract surgery.¹

Disease recurrence

Due to disruption of the blood-ocular barrier and promotion of inflammation during surgery, patients run the risk of suffering disease recurrence following cataract surgery. Some cases may require increasing immunosuppression to regain adequate control. However, current prophylactic measures have overall been successful in preventing recurrence of inflammation. A recent longitudinal study by Sharief et al. examined outcomes of 309 eyes of uveitic patients who underwent phacoemulsification with IVTA or postoperative oral prednisolone, compared to a control group that remained phakic. At five-year follow-up, pseudophakic eyes had no significant increase in uveitis relapse or change in dosing of topical or systemic steroids compared to pre-surgery period or control eyes.⁸

Present relevance and future avenues to investigate

A suprachoroidal formulation of triamcinolone has been developed in the search for a treatment modality that limits the undesirable side effects of steroids, but still provides adequate drug concentrations to the posterior segment. In 2018, Yeh et al. summarized findings of a randomized, controlled study that followed 17 patients with macular edema due to noninfectious uveitis who received a single suprachoroidal injection of 4.0 mg triamcinolone.³⁷ Importantly, patients who had a history of steroid-refractory disease were excluded from this study. In comparison to the control group who received a dosage of 0.8 mg, the treatment group experienced both statistically and clinically significant decreases in retinal thickness, improvement of visual acuity, and reduction of anterior chamber and vitreous inflammation over a two-month follow-up period. Adverse events were uncommon and largely injection-related, including eye pain at the time of injection and conjunctival hemorrhage, but no serious ocular effects were noted in follow-up, including elevation of intraocular pressure. This suggests that suprachoroidal drug delivery may be a viable future alternative for uveitic macular edema, though comparative trials with greater enrollment and longer follow-up are needed to determine whether reinjection is necessary, to explore the relative safety and efficacy of suprachoroidal injections to existing periocular and intravitreal options, and to elucidate if IOP elevation and glaucoma may still develop in the long term.

Several steroid-sparing agents are being studied to provide alternative options for preventing and managing refractory CME. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is currently being investigated with some success reported for patients with refractory pseudophakic CME, for whom it is thought a need exists to stabilize the blood-retinal barrier by multiple mechanisms.³⁸ Most studies report results with bevacizumab, which has been associated with decreased mean macular thickness in patients with CME unresponsive to conventional treatment, including intensive topical steroids and NSAIDs, and periocular and intravitreal steroids.^38-44 One study has reported the use of bevacizumab as an effective primary treatment for pseudophakic CME.⁴⁵ For some, effect was dramatic and rapid, with resolution of chronic CME occurring within two weeks following one injection of anti-VEGF, and sustained in follow-up up to 12 months.^40,43 Other studies report response only after repeated injections.^38,43 No significant adverse events have been reported with intravitreal anti-VEGF injections in these patients. However, there appears to be significant variability in improvement of visual acuity, though this may be a function of the chronicity of underlying pathology. Ranibizumab has been studied in a relatively large randomized, controlled study of 156 patients with macular edema of uncommon etiologies; variable effects were seen amongst subgroups, with greater than one line improvement in visual acuity observed in patients with inflammatory conditions and post-cataract surgery.⁴⁶ Overall, the evidence remains scant, and further studies are needed to establish the role of anti-VEGF agents for refractory pseudophakic CME.⁴⁷ It has not yet been determined whether intravitreal anti-VEGF may play a role in preoperative or intraoperative prophylaxis.

A few reports of intraocular methotrexate suggest some efficacy for inflammation and uveitic macular edema. In a study by Hardwig et al., eight out of nine patients with uveitis treated with intravitreal methotrexate showed improvement in visual acuity, out of which three out of four patients with pre-existing CME achieved VA of 20/ 20.⁴⁸ Another study by Taylor et al. of 15 eyes with exacerbation of noninfectious intermediate, posterior, or panuveitis and/or CME reported improvement in VA and ocular inflammation after intravitreal methotrexate, with a decrease in dose of systemic immunosuppression. Relapse after four months was noted in some patients, but reinjection of methotrexate had similar efficacy.⁴⁹ No adverse events have yet been reported with these injections, and intraocular methotrexate thus may represent an additional steroid-sparing option for patients with refractory uveitis and CME.

Systemic therapies for uveitic and pseudophakic CME currently being explored include acetazolamide, subcutaneous interferon, and subcutaneous somatostatin. Oral acetazolamide has historically been attempted with variable success in small cohorts; studies of patients with uveitic or pseudophakic macular edema have found a decrease in CME that may or may not ultimately affect visual acuity ^{50, 51}. Subcutaneous interferon-alpha 2a and 2b injections have shown efficacy in small case series of patients with pseudophakic or uveitic macular edema refractory to topical NSAIDs, intravitreal anti-VEGF, acetazolamide, intravitreal triamcinolone, systemic steroids, and immunosuppression.^52,53 The studied regimen for these interferon injections often consist of a treatment dosage of 3 or 6 million IU once or twice weekly for four weeks with a slow taper over months. Resolution of CME is noted within days and maintained up to six months after treatment in patients whose disease is refractory to one or more immunosuppressive agents.^54-56 The recent BIRDFERON study evaluated 48 patients with chronic bilateral noninfectious uveitis complicated by macular edema who were randomized to treatment with subcutaneous interferon or systemic corticosteroids, or no treatment; comparable improvement in CME was observed in both treatment groups compared to controls.⁵⁷ Mild side effects, including fatigue, malaise, arthralgia, nausea, anorexia, and hair loss, have been reported with these injections, as well as serious adverse events, such as pancreatitis, necessitating discontinuation of therapy.^56,57 Of note, use of an eyedrop formulation of interferon alpha 2b was described in a 2018 case report of a patient with refractory pseudophakic CME; complete resolution of CME with 1 MIU/mL four times daily was reported after 12 weeks, with stability at 36-week follow-up.⁵³ Finally, subcutaneous octreotide, a somatostatin analogue, has also demonstrated benefit for uveitic CME resistant to periocular and systemic therapies in case reports and small case series. Missotten et al. conducted a study of 20 patients with refractory CME treated with long-acting octreotide injections, with reduction of CME reported in 70% of episodes within two to four months.⁵⁸ Of note, recurrence of CME occurred in about 30% with discontinuation of treatment, suggesting patients may require repeat injections for sustained effect. However, amongst those who were successfully treated, nearly 40% maintained resolution of CME for more than one year.

To this day, cataract extraction in uveitic patients remains a unique challenge. Certain principles are clear in approaching these patients, including controlling inflammation for at least three months before surgery to optimize structural and functional outcomes following surgery. However, despite the well-known susceptibility of uveitic patients for postoperative CME, no clear algorithm exists for the prophylaxis of CME or treatment of refractory CME in this susceptible population, and this represents an avenue of research that could have significant bearing upon these patients’ post-surgical outcomes. In this article, we have described the literature on established as well as alternative modalities for treating pseudophakic CME in uveitis patients, but we recognize that much of the data comprise small case series, case reports, and uncontrolled studies. Interpretation of data, therefore, must be performed with caution given the small number of subjects and heterogeneity of existing studies. Ultimately, this highlights the need for larger studies and, specifically, randomized clinical trials, which is particularly challenging as uveitic patients represent a relatively small subset of the population undergoing cataract extraction. POINT (Periocular and Intravitreal Corticosteroids for Uveitic Macular Edema Trial, NCT02374060), was a recently completed trial headed by Jabs that evaluates the relative efficacy of periocular triamcinolone, intravitreal triamcinolone, and the intravitreal dexamethasone implant in patients with macular edema secondary to uveitis; results are pending at the time of this publication. Some other ongoing clinical trials include SOAP (Study for Optimizing Anti-inflammatory prophylaxis, NCT03383328), which evaluates the timing of topical NSAIDs, as well as their efficacy in comparison to topical prednisolone and intraoperative sub-Tenon dexamethasone; ACME (Treatment of Macular Edema After Cataract Surgery with Subconjunctival Aflibercept, NCT03396861), which studies the utility of subconjunctival aflibercept for pseudophakic macular edema unresponsive to topical therapy; MEND (Macular Edema Nepafenac vs. Difluprednate Uveitis Trial, NCT01939691), which compares the use of various individual and combinations of topical nepafenac, difluprednate, and prednisolone for uveitic macular edema; and MERIT (Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial, NCT02623426), which compares the relative efficacy and safety of the dexamethasone implant, intravitreal methotrexate, and intravitreal ranibizumab for uveitic macular edema refractory to intravitreal steroids.

Summary

Uveitis patients represent a unique subset of the population undergoing cataract surgery and pose several challenges that require special consideration and strategy. Control of inflammation should be prioritized to promote successful cataract extraction, maximize visual outcomes, and minimize postoperative complications for patients with uveitis. Traditionally, this has been accomplished with intensive topical, oral, or intravenous steroids in the preoperative period, as well as intraoperative intracameral or intravitreal triamcinolone or longer-acting steroid implants, though the steroid burden subjects these patients to significant risk of intraocular pressure elevation. With current prophylactic measures, structural and functional outcomes post-surgery may be comparable to those for the non-uveitic population, but patients with a history of uveitis still remain at higher risk for postoperative CME, and no clear algorithm exists for the prophylaxis against or management of refractory pseudophakic CME. Intravitreal anti-VEGF and methotrexate, oral acetazolamide, and subcutaneous inferferon alpha and somatostatin have all been reported to reduce and even resolve refractory cases of pseudophakic and uveitic macular edema, and may represent options for CME that does not respond to the standard topical, periocular, intravitreal, and systemic steroids. However, more studies are needed to establish the potential efficacy and role of these agents in the perioperative management of uveitic cataracts.

KEY POINTS.

• Control of inflammation should be prioritized to promote successful cataract extraction, maximize visual outcomes, and minimize postoperative complications for patients with uveitis.

• No clear algorithm exists for the prophylaxis against or management of refractory pseudophakic cystoid macular edema in this susceptible population.

• Further studies are needed to establish the efficacy and role of steroid-sparing agents, including intravitreal anti-VEGF and methotrexate, oral acetazolamide, and subcutaneous interferon alpha and somatostatin, for refractory postoperative cystoid macular edema.