Cataract Surgery and Diabetic Retinopathy

10.1Scope of the Problem of Diabetic Retinopathy Concomitant with Surgical Cataract

Diabetes mellitus is increasing around the world with 171 million affected persons in 2000 and projected prevalences of 221 and 366 million affected patients by 2010 and 2030, respectively.1,2 In the United States, an estimated 7.8% of the population has diabetes.3 Diabetic patients have an increased risk of developing cataract and develop cataract at an earlier age than patients without diabetes.1,4–8 In developed nations, 11–25% of all cataract surgery is performed in patients with diabetes and 1.2–5.0% of these patients will have concomitant diabetic retinopathy.7,9–13 Thus, cataract surgery in patients with diabetes and with diabetic retinopathy is common, yet the interactions of cataract surgery and the diabetic eye are incompletely understood and a subject of controversy.

diabetes but no retinopathy.14–19 Visual acuity outcomes of cataract surgery are worse in patients with diabetic retinopathy than in patients without diabetic retinopathy. In patients with nonproliferative diabetic retinopathy (NPDR), rates of visual acuity 20/40 have been reported from 52 to 70% and are worse the more severe the retinopathy, because increasing severity of retinopathy is asso-

ciated with increasing prevalence of diabetic macular edema (DME).16,19–25 In patients with treated

proliferative diabetic retinopathy (PDR), rates of

postoperative visual acuity 20/40 have been reported from 26 to 53%.19,23,26 Visual acuity

outcomes after cataract surgery are worse in patients with preoperative DME because of postoperative exacerbation of the edema and are worse in older patients because of higher

rates of development of postoperative macular edema (Table 10.1).16,20,24,25,27

10.2Visual Outcomes After Cataract Surgery in Patients with Diabetic Retinopathy

The rate of visual outcome 20/40 in patients without diabetes who undergo cataract surgery is 85%, and similar rates apply to patients with

D.J. Browning (*)

Charlotte Eye Ear Nose & Throat Associates, Charlotte, NC 28210, USA

e-mail: dbrowning@ceenta.com

10.3Postoperative Course and Special Considerations After Cataract Surgery in Patients with Diabetic Retinopathy

Uneventful cataract surgery in patients with diabetes has been inconsistently associated with higher rates of posterior capsular opacification and lower postoperative endothelial cell counts than in patients without diabetes.28–32 Patients with diabetes have more anterior chamber inflammation after cataract surgery and a greater tendency to develop iris synechia and capsulorhexis contraction

Table 10.1 Rate of visual acuity 20/40 by retinopathy severity

DME ¼ diabetic macular edema. PDR ¼ proliferative diabetic retinopathy.

Reproduced with permission from Dowler.27 Table summarizing visual outcomes of cataract surgery in patients with diabetes by retinopathy severity and presence or absence of preoperative macular edema.

than patients without diabetes.16,32–34 These differences seem more pronounced with extracapsular and intracapsular cataract extractions and have not been as apparent with phacoemulsification and small incisions, the contemporary preferred technique.30,35–37 More postoperative inflammation is noted in eyes with more advanced retinopathy, especially in eyes with active proliferative retinopathy. This may be related to the increasing breakdown of the blood–aqueous barrier that parallels increasing retinopathy severity.25,38 The creation of a larger anterior capsulorhexis and the use of a more intense postoperative anti-inflammatory drop regimen than in nondiabetics have been recommended to aid in visualizing the peripheral fundus and to prevent synechiae, respectively.39,40 Intraocular lenses with larger optics and no positioning holes are recommended to allow easier panretinal laser treatment, based on less peripheral capsular opaci-

fication and a greater optical area for viewing the fundus, should it be needed.36,39–41 Anterior cham-

ber lenses are not advised because of the increase in anterior chamber inflammation associated with haptic chafing. Silicone intraocular lenses should be avoided because they develop more inflammatory cellular precipitates than acrylic and polymethylmethacrylate lenses, suffer worse condensation on the posterior lens surface in the presence of an open posterior capsule during air–fluid exchange in vitrectomy surgery, and adhere to

silicone oil after YAG capsulotomy, should the use of oil be needed later.42,43 Larger YAG laser

capsulotomies are recommended to facilitate possible later panretinal laser treatment.16

Patients with diabetic retinopathy can develop

iris neovascularization (NVI) after cataract sur- gery.16,44–48 The risk of this complication is

increased if the posterior capsule is opened, but it

occasionally develops with uncomplicated surgery and an intact capsule.20,43,45,49 It was much more

common in the era of intracapsular surgery, with a reported incidence of 7.8–8.9% in series with no selection for degree of preoperative retinopathy severity.44,49 In the era before endolaser photocoagulation, eyes undergoing lensectomy in addition to vitrectomy for proliferative diabetic retinopathy had a threefold increased risk of developing postoperative NVI.50 Careful inspection for any retinal neovascularization before cataract surgery or YAG capsulotomy is important, and panretinal laser photocoagulation should be applied before either procedure if new vessels are discovered.36,43

Rarely, cataract surgery must be performed in an eye with active NVI, because no view to the fundus is possible. Preoperative intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs such as bevacizumab causes rapid involution of the new vessels, reduces intraoperative bleeding, and allows intraoperative photocoagulation to be

applied to enable more sustained regression of the new vessels.51,52 At the end of surgery, a repeat

injection of bevacizumab may be advisable because the effect of scatter photocoagulation is not immediate.

Some patients with advanced diabetic retinopathy require pars plana vitrectomy. Vitrectomy surgery can accelerate progression of cataract and

lead to a subsequent need for cataract surgery.53,54 The visual prognosis in such cases is

guarded because of the limitations imposed by the underlying retinopathy, but 90% of eyes can expect improved visual acuity after cataract sur-

gery and 45–50% can expect an outcome 20/ 40.26,54,55 In addition, the technical aspects of the

surgery can be different, including significant intraoperative fluctuations in anterior chamber

depth, unexpected zonular dehiscence, and higher rates of a dropped nucleus.36,54,55 In some

patients, combined cataract surgery and vitrectomy may be needed because of concomitant cataract and active proliferative retinopathy with vitreous hemorrhage. As in the case of NVI,

preoperative use of anti-VEGF drugs can reduce the risk of intraoperative bleeding, but anecdotal

evidence suggests that any pre-existing retinal traction may be worsened with these agents.56,57

10.4The Influence of Cataract Surgery on Diabetic Retinopathy

It has been long suspected that intracapsular and extracapsular cataract surgeries can exacerbate

diabetic retinopathy, but relevant evidence has been inconsistent.9,21,23,24,34,48,58–67 The more

recent literature, applicable to phacoemulsification, supports the view that, on average, uncomplicated surgery does not cause clinically important retinopathy progression when the

preoperative retinopathy is less advanced than

severe nonproliferative.1,9,10,30,37,58,60,62,64,68–73

There are, however, exceptional case reports in which exacerbation of retinopathy has occurred with contemporary, uncomplicated phacoemulsification technique.74 Preoperative presence of diabetic retinopathy, duration of diabetes, worse glycemic control, surgery by residents, and use of insulin have been reported as risk factors for pro-

gression of retinopathy after cataract surgery.23,30,34,73 There is little evidence regarding the

effect of uncomplicated phacoemulsification surgery on retinopathy progression in eyes with untreated severe NPDR or PDR because of clear evidence of retinopathy progression from the era of intracapsu-

lar or extracapsular surgery and therefore intentional avoidance of this situation.20,44,48,75 In a series of eyes

undergoing intracapsular cataract extraction in the presence of active PDR, 20% developed vitreous hemorrhage within 6 weeks of surgery.44 This has been extrapolated to the phacoemulsification era, and such eyes are typically treated with panretinal photocoagulation (PRP) first to reduce the levels of intraocular angiogenic growth factors before cataract surgery.20 There is evidence, however, that uncomplicated phacoemulsification cataract

surgery can be associated with the induction or exacerbation of DME.62,63,68–70,76–78 Little evi-

dence exists associating uncomplicated phacoemulsification cataract surgery and exacerbation

of macular ischemia in patients with diabetic reti-

nopathy, although reports existed of this association after extracapsular surgery.20,64,66,79 Before

the phacoemulsification era, anterior segment neovascularization was reported to follow cataract surgery in 6–8% of cases with most of the evidence

implicating primary capsulotomy as increasing the incidence of this complication.20,44,49 The rate has

been less since the widespread adoption of phacoemulsification.

The association between cataract surgery and development or exacerbation of macular edema in diabetics is complicated to unravel because there are two types of macular edema in these situations – pseudophakic cystoid macular edema (PCME) and DME. In patients without diabetic retinopathy undergoing uncomplicated cataract surgery, the rate of clinically recognized macular

thickening due to perioperative inflammation, PCME, has been reported to be 1–5%.34,80–82

PCME usually spontaneously resolves within 6 months.83,84 Uneventful cataract surgery in nondiabetics who do not develop PCME is generally associated with a mild, clinically unimportant, and

transitory increase in macular thickness less than 10 mm.80,81,84–87 Patients with diabetes have higher rates

of PCME ranging from 13 to 24% in different series, and more severe retinopathy at baseline has been

associated with higher postoperative rates of PCME.34,59,73,81,82,88–90 Rates of fluorangiographic

but not clinical PCME are also higher in eyes of diabetics undergoing cataract surgery than in eyes of nondiabetics and higher than rates of clinical PCME. In eyes of patients with diabetes but no retinopathy, rates of fluoroangiographic PCME at 1 month and 1 year were 69% and 24% for diabetics without retinopathy compared to 63% and 0% for nondiabetic eyes, respectively.90 Patients with pre-existing diabetic retinopathy who develop PCME are more recalcitrant to treatment than those who do not have pre-existing diabetic retinopathy.91

DME considered as distinct from PCME can be induced or exacerbated by cataract surgery, with

reported rates that vary according to many variables.21,27,59,63,64,71,77 Diabetes causes a breakdown

of the blood–ocular barrier before overt retinopathy is seen.31,37,92 Vascular permeability increases

with increasing retinopathy severity. Increased

intraocular concentrations of inflammatory cytokines associated with cataract surgery added to the diathesis of increased permeability in diabetes

translate into an increased incidence of postcataract surgery macular thickening.64–66,70,77,93 Patel

and colleagues prospectively assessed aqueous humor concentrations of growth factors after uncomplicated cataract surgery in seven eyes of six patients with diabetic retinopathy. Pro-angio- genic growth factors (VEGF, hepatocyte growth factor (HGF), and interleukin 1b (IL-1b)) and anti-angiogenic growth factors (pigment epithe- lial-derived growth factor (PEDF)) were assayed. VEGF, IL-1b, and PEDF rose at 1 day after surgery and declined by 1 month. HGF increased progressively over the first month after surgery. One patient developed DME. Although the number of eyes studied was small, the evidence suggests a possible mechanism for the development or exacerbation of DME after cataract surgery. Others have reported elevated intraocular levels of leukotrienes and endothelin after cataract surgery, which could enhance breakdown of the blood–retina barrier.66 Surgically induced inflammation is less with small incision phacoemulsification than large incision extracapsular or intracapsular technique, which may explain the clinical impression that exacerbations of DME by cataract surgery are less common in the phacoemulsification era.94 Rapid control of diabetes shortly before performing cataract surgery has been associated with an increased risk of new DME or exacerbation of pre-existing DME in the 12 months following uncomplicated cataract surgery and should be avoided.78

It can be difficult to define postsurgical

increases in macular thickness as purely PCME or as purely DME.20,66,95 Presence of disk hyperfluor-

escence on fluorescein angiography has in the past been said to be helpful in distinguishing DME from PCME, but the observation in prospective studies that the optic disk becomes more hyperfluorescent after cataract surgery in diabetic eyes that do not develop clinical macular edema undermines the usefulness of this suggested pearl.70,96 Dowler and colleagues did not find that disk hyperfluorescence allowed discrimination of PCME from DME.68 Presence of associated hemorrhage and lipid, a multifocal rather than a foveocentric pattern of

edema, and petalloid late macular staining may help to distinguish DME from PCME, but again

are subjective signs of questionable reliability (Fig. 10.1).9,36,64,96 Thus, the relative contributions

of DME versus PCME in postsurgical macular

thickening can be difficult to assess in mixed clinical pictures.9,96 In the past, when it was thought

that the treatments differed for the two conditions, discriminating the components had greater importance. With the discovery that anti-inflammatory drugs can improve DME and that anti-VEGF

drugs can improve PCME, the importance of the distinction has diminished.82,97–101

Eyes of diabetics with a range of retinopathy severities and no clinical DME preoperatively develop postoperative macular thickening that is greater than that of nondiabetics undergoing uncomplicated cataract surgery. Table 10.2 shows the results of four prospective studies involving a total of 160 eyes with average grades of retinopathy severity ranging from no-DR to mild NPDR before surgery. At 1–3 months after surgery, the macular thickness increase ranged from 10 to 69 mm and more

severe retinopathy was associated with a larger increase in macular thickness.70,77,93,102 Thus,

even in diabetic eyes without clinical macular edema after cataract surgery, subclinical edema predictably develops. None of these studies makes an attempt to distinguish the macular thickening associated with the cataract surgery as PCME or DME.

Prospectively acquired data on the effect of cataract surgery on DME are available from the Early Treatment Diabetic Retinopathy Study (ETDRS) in which 81% of 270 eyes of 205 patients had laser photocoagulation for DME or PDR before cataract surgery.58 In this series, there was no adverse effect of cataract surgery on the prevalence of DME. The proportions of eyes with photographically documented clinically significant diabetic macular edema (CSME) at the nearest annual visit were 29% before cataract surgery and 31% after cataract surgery.58 The authors attributed this lack of effect of cataract surgery on rates of CSME to the high rate of preoperative macular laser treatment.58 This publication has been the basis for the widely accepted principle that in a patient with concomitant surgical

Fig. 10.1 A 67-year-old man with mild NPDR and no macular edema had20/50 bestcorrectedvisualacuityoftheright eyeanda visually significant cataract. A preoperative OCT on April 25, 2007,showednomacularedema(Panelsaandb).Uncomplicated phacoemulsification cataract extraction with posterior chamber intraocular lens implant on May 30, 2007, was followed by macular edema that was considered to be purely postoperative PCME. The disk was hyperfluorescent and the pattern of late macular

hyperfluorescence was petalloid (Panel c). It did not respond to topical prednisolone acetate and ketorolac therapy, but did respond to intravitreal triamcinolone injection, 4 mg. It reoccurred and responded to posterior subtenon’s triamcinolone injection, 40 mg. The macular edema reoccurred 6 months later, andconsiderationwasgiventothepossibilitythatthiswasatleast in part DME and not PCME. Focal laser photocoagulation was given to the leaky microaneurysms on September 9, 2009

cataract and CSME, the DME should be treated with focal/grid laser until it resolves or until maximal treatment has been applied before cataract surgery is performed. If this management pathway has been followed, on average one can expect that the cataract surgery will not adversely affect the prevalence of macular edema. An example of this common situation is illustrated in Fig. 10.2 in which an eye has been treated with maximal laser, continues to have DME, and yet does not have the feared exacerbation of edema by cataract surgery. There are, however, particular patients in which worsening will occur and adjunctive pharmacologic treatments may have a role in these cases.

One prospective study has suggested a difference in course for DME existing before cataract surgery and that developing de novo after surgery.68 The edema occurring de novo after surgery has been hypothesized to be PCME, which is known to spontaneously remit in a high percentage of cases.83 De novo CSME developed in the first year after cataract surgery in 13 of 27 (48%) eyes.68 In 9 of these 13 eyes (69%), this CSME resolved spontaneously within the first postoperative year.68 None of five eyes with preoperative CSME showed spontaneous resolution.68 Some have suggested that macular edema in eyes with diabetic retinopathy after cataract surgery

be treated as PCME for 3–6 months, and then treated as DME if it persists beyond 6 months.9,41,103

Fig. 10.2 In this figure, the Y-axis represents central subfield mean thickness in microns (CSMT). The X-axis represents time of follow-up (months), and illustrative OCT studies over the 4-year span illustrated are shown below at the times corresponding to the graphed CSMTs. Associated best corrected visual acuities are shown beneath the false color maps. This 66-year-old woman developed DME in 2004 and despite multiple focal laser treatments, some with adjunctive intravitreal bevacizumab (Avastin) and triamcinolone, continued to have refractory DME. Cataract developed, accelerated by the triamcinolone, and she underwent uneventful phacoemulsification with posterior chamber intraocular lens implantation 4 years later. Because her DME had been refractory to previous intravitreal triamcinolone injection,

no repeat injection was given immediately preceding her surgery, and no worsening of the DME was noted after cataract surgery. Refractory, persistent DME remains, but the patient is content with her improved visual acuity following surgery and prefers no further intravitreal injection therapy although the option was presented. Vitrectomy surgery was also presented as a possible option should the DME worsen and vision decline, but was not recommended in this eye with visual acuity of 20/32. F=focal laser photocoagulation; BF=intravitreal bevacizumab injection followed by focal laser treatment 1 week later; TF= intravitreal triamcinolone injection followed by focal laser treatment 1 week later; C=cataract surgery

Fig. 10.3 Example of a patient in whom de novo macular thickening following cataract surgery was unlikely to be PCME and in which a favorable outcome followed

treatment of leaking microaneurysms under the alternate assumption that the situation represented DME instead