Retinal Challenges

Educational Objectives

The goal of this program is to improve the diagnosis and management of patients with retinal disease. After hearing and assimilating this program, the clinician will be better able to:

1.   Identify those patients with cataracts who would benefit from preoperative retinal testing, evaluation, and treat­ment.

2.   Describe the efficacy of intravitreal steroids for managing diabetic macular edema (DME).

3.   Describe the efficacy of laser photocoagulation for managing DME.

4.   Recognize risk factors for development of choroidal neovascularization (CNV) in patients with dry age-related macular degeneration.

5.   Evaluate the efficacy of common treatments designed to prevent CNV.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning com­mittee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose Dr. Snady-McCoy presents information in her lecture that is related to off-label or investigational use of a therapy, product, or device.

Acknowledgments

Dr. Snady-McCoy was recorded at the 725th Meeting of the New England Ophthalmological Society, presented May 29, 2009, in Boston, MA, by the New England Ophthalmological Society, Inc.; Dr. Schachat was recorded at the 3rd Annual Innovations in Ophthalmology, presented March 16-19, 2009, in Key Largo, FL, by the Cole Eye Institute of Cleveland Clinic, Cleveland, OH. The Audio-Digest Foundation thanks the speakers and the sponsors for their coop­eration in the production of this program.

When Should I Send My Patient for Retinal Evaluation Before Cataract Surgery?

Lory C. Snady-McCoy, MD, Clinical Associate Professor of Ophthalmology, Alpert Medical School, Brown University; Chief of Ophthalmology, Women and Infants Hospital; Director of the Retinal Service, Rhode Island Hospital, Providence, RI

Age-related macular degeneration (AMD)

Age-Related Eye Disease Study (AREDS): Chew et al, 2009; overview  —  increase in AMD after cataract surgery not verified; use of UV-B lenses possible contributing factor; findings  —  no statistical increase in AMD in cata­ract surgery group vs nonsurgery group (exception matched-pairs analysis); AMD advanced in nonsurgery eyes due to natural course of disease; current cataract surgery techniques do not increase risk for AMD; caveat  —  optical coherence tomography (OCT) not used in AREDS (in some patients, neovascular AMD missed by fluo­rescein angiography; OCT may detect these, especially in high-risk patients)

Evaluation of patients with AMD before cataract surgery: utilize tests to obtain best baseline and allow  anticipation of undesired result; pretreat with anti-vascular endothelial growth factor (VEGF)

Diabetic Retinopathy

Postoperative diabetic macular edema (DME): incidence twice that of nondiabetic ME (22%); usually, ME lasts >3 mo (often requires long-term therapy); the longer ME lasts, the less likely it will resolve; risk factors  —  diabetes >10 yr; insulin dependence; previous macular laser therapy (indicating previous ME); level of retinopathy (mod­erate-to-severe retinopathy at greatest risk; risk small for patients with no retinopathy); other risk factors  —  medical complications of diabetes, male sex, and exposure to pentosidine

Prevention of DME: net gain in visual acuity (VA) smaller after cataract surgery in eyes with more severe diabetic retinopathy; in natural course of disease, retinopathy worsens over time; scattered reports worldwide show less severe postoperative DME and better visual outcome in patients receiving sub-Tenons or intravitreal triamcino­lone (Kenalog) at time of surgery; bevacizumab (Avastin)  —  results similar (patient numbers small); if DME not controllable preoperatively  —consider sub-Tenons injection of triamcinolone

Nonsteroidal anti-inflammatory drugs (NSAIDs): in 2 studies, use of NSAIDs in diabetic eyes after cataract sur­gery beneficial; use of topical steroids  —  in 1 study, intraocular pressure (IOP) increased; steroids clearly not as beneficial as NSAIDs; another study showed benefit in decreasing DME (most eyes required >3 mo treatment); eyes with persistent DME >24 mo necessitated chronic topical steroid therapy; often, if therapy discontinued, DME recurred; conclusions  —  postoperative NSAIDs helpful, and duration of use longer in diabetic patients

More management tips: preretinal fibrosis and vitreoretinal traction important causes of DME (OCT important in these eyes); study from Hungary (2008)  —  macular traction may contribute to DME in up to 32% of cases (pa­tients best treated with combined cataract surgery and vitrectomy, especially those with vitreomacular traction)

Risk for retinal detachment (RD) after cataract surgery in patients with high myopia

Study from Mayo Clinic (2006): incidence of RD increased 4-fold, compared to nonsurgery eyes (from 0.27% at 1 yr to 1.8% at 20 yr); no difference in risk between phacoemulsification and extracapsular cataract extraction

Risk factors: age  —  in 2008 study from New Zealand, 4% incidence of RD in postsurgical eyes (greatest risk in pa­tients <50 yr of age; risk small at >70 yr of age [RD usually occurs after posterior vitreous detachment]); other risk factors  —  include posterior capsular tear, RD in fellow eye, increased axial length, and male sex; incidence of RD in eyes with long axial length 1.3% to 4% (risk increases with time after surgery); mean time of occur­rence of RD 2 to 3 yr postoperatively (incidence highest in patients <50 yr of age)

Best course of action: know risk factors; educate patients about symptoms; monitor patients carefully, especially during first 3 yr after cataract surgery; treat pathology as it occurs (treatment usually successful)

Epiretinal membranes

Overview: predicting outcome challenging in patients with epiretinal membranes and cataracts (research nonexis­tent); epiretinal membranes can be mild and surface-related, or more severe with vitreoretinal traction; preva­lence of epiretinal membranes in general population 12%

Risk factors: age (incidence 2.7% in 43- to 54-yr agegroup, 12.8% at >75 yr of age); retinal pathology (eg, retinal vascular disease, branch retinal vein occlusion, diabetic retinopathy [especially proliferative form]); previous cat­aract surgery; negative association with AMD; no associated systemic factors

Current Concepts in the Management of Diabetic Macular Edema

Andrew P. Schachat, MD, Vice Chair of Clinical Affairs and Director of Clinical Research, Cole Eye Institute, Cleveland Clinic, Cleveland, OH

Epidemiology: DME leading cause of new blindness in working-age Americans

Early Treatment Diabetic Retinopathy Study (ETDRS)

Overview: issue whether laser photocoagulation effective for treatment of DME; laser treatment reduces rate of mod­erate visual loss by 50% compared to no treatment

Parameters: study looked at patients with mild-to-moderate nonproliferative diabetic retinopathy and DME; one-half of subjects assigned to initial focal laser treatment; treatment protocol  —  treat all treatable lesions within 2 disc diameters (DD) of center but ³500 mm from center; apply laser using small spot and short duration (repeat as needed until color change seen); in areas without microaneurysms, perform mild grid treatment in areas of diffuse leakage or nonperfusion; treatable lesions  —  areas of diffuse leakage (microaneurysms, intraretinal microvascular abnormalities, or diffusely leaking capillary bed); retinal avascular zones; repeat every 4 mo if clinically significant ME persists; primary end point  —doubling of visual angle or 15-letter loss on ETDRS chart; results  —  using ET­DRS protocol, risk for decrease in VA reduced by one-half, but only »10% of patients improved

Intravitreal Steroids

Intravitreal triamcinolone acetonide for treatment of refractory diabetic macular edema (Yilmaz et al, 2009): systematic review; VA improves initially; many side effects; LogMar outcomes at 1 mo  —  statistically significant improvement; at 3 mo  —improvement wearing off; at 6 mo  —  further regression (benefit essentially insignificant); with retreatment, side effect profile worse; side effects  —  »30% of patients experience elevated IOP; nearly 100% develop cataract; incidence of endophthalmitis 1.0% (vs 0.10% from intravitreal anti-VEGF injections)

Intravitreal triamcinolone compared to focal/grid photocoagulation for DME (Diabetic Retinopathy Clinical Research [DRCR] Network, 2008): eyes randomized to focal/grid photocoagulation, 1 mg triamcinolone, or 4 mg triamcinolone; new or persistent edema retreated at 4-mo intervals; results  —  at 4 mo, VA in steroid group better than laser group, but with longer follow-up, no difference; at 16-mo and 2-yr follow-ups, laser-treated group had better vision; VA at 2 yr  —  on average, laser group gained 1 letter, and steroid groups lost some letters; subgroups  —  if initial VA good (ie, 20/30 to 20/60), not much room for improvement; improvement greater if initial vision 20/60 to 20/320; comment  —  laser treatment with DRCR protocol about as effective as in ETDRS; DRCR studied “all comers” (overall, patients had poorer vision at baseline; 80% of patients in ETDRS had better than 20/40 VA at baseline); patients with 20/25 VA cannot improve 3 lines; if only eyes with VA worse than 20/40 at baseline consid­ered, »40% of patients in ETDRS who received laser photocoagulation gained ³6 letters at 3 yr; so, report of im­provement in only 10% of patients in ETDRS related to relatively good initial vision in 80% of participants; looking at comparable patient groups  —  DRCR study had almost same result with laser at 2 yr as ETDRS (47% im­proved with laser treatment; 71% avoided vision loss or remained stable)

Conclusion: based on long-term outcomes, steroid therapy does not make sense; laser therapy using ETDRS protocol standard of care; steroid therapy has short-term efficacy and poor safety; anti-VEGF drugs may prove better option (more research needed); in 1963, risk for blindness in patients with diabetic retinopathy 50% (by applying regimen used in ETDRS, rate only 1% or 2%)

Laser Treatment for Dry Age-related Macular Degeneration

Dr. Schachat

Background: large drusen, large area of drusen, and hyperpigmentation over drusen key predictors of choroidal neo­vascularization (CNV); low-power laser therapy can achieve regression of drusen; issue  —  does laser prophylaxis reduce risk of developing CNV? (answer: no)

Risk factors for CNV

Overview: large bilateral drusen  —  for patients ³65 yr of age, risk for CNV 2% to 9% per year (5-yr risk 10%-50%); CNV in fellow eye  —  risk higher; if first eye has scar or CNV and second eye has large drusen, risk 5% to 12% per year (5-yr risk 25%-60%); vitamin supplementation (data from AREDS)  —  on placebo, 5-yr risk of de­veloping advanced AMD 28% (with supplementation, risk reduced one-quarter to one-third)

Key predictors of CNV: area of drusen (difficult to estimate); maximum drusen size less reliable, but still useful predictor (larger drusen, greater risk); hyperpigmentation over drusen increases risk for CNV 2- to 2.5-fold; rela­tive risk  —  if drusen absent or questionable and no hyperpigmentation present, risk 1% per year (5-yr risk 5%); with largest drusen and no pigment, 5-yr risk 35%; large drusen and moderate-to-severe hyperpigmentation worst combination (risk 10% per year; 5-yr risk »50%)

More about AREDS: no drusen or hyperpigmentation  —  risk for CNV 1% per year; with vitamin and mineral sup­plementation, risk still 1% per year (no benefit); drusen at least moderate in size and area  —  supplementation recommended (use of AREDS protocol can achieve 30% reduction in risk for CNV); potential impact on public health (Lanchoney et al, 1998)  —  30% reduction in risk for CNV would reduce AMD-related blindness by »50%; AREDS protocol includes beta carotene (contraindicated in cigarette smokers)

Choroidal Neovascularization Prevention Trial (CNVPT; 1998, 1999, 2001): parallel studies  —  unilateral treat­ment of bilateral large drusen; fellow eye trial (unilateral treatment of drusen in patients with CNV in fellow eye); results  —regression achieved and contrast sensitivity improved in eyes with significant drusen; however, enrollment discontinued early in fellow eye study because of increased CNV at 12 mo (laser treatment harmful); rates of CNV  —  in fellow eye trial, 17% of treated eyes and 3% of controls developed CNV by 12 mo; by 30 mo, incidence of CNV same; in bilateral trial, 1% of treated eyes and »2% of controls had CNV (hint of benefit)

Prophylactic treatment of AMD (Friberg et al, 2006): study looked at subthreshold (low level) laser therapy in 2 trials; fellow-eye trial (2006)  —  244 subjects; with lower power, treated eyes had increased rate of CNV (15% vs 1%; VA also worse); bilateral trial (1999)  —  drusen reduced; at 3 yr, CNV rates did not differ; larger study needed; paper presented at Association for Research in Vision and Ophthalmology (ARVO)  —  in some subgroups, mild VA benefit

Laser treatment in patients with bilateral large drusen: complications of age-related macular degeneration prevention trial (CAPT, 2006): assumptions  —  good data that treating fellow eyes with laser not safe; but low en­ergy laser treatment in bilateral cases seems safe, and even moderate benefit would have large public health impact; parameters  —  1052 subjects with bilateral large drusen enrolled; percentage of eyes with ³50% reduction in drusen  —  early on, many more treated patients had regression of drusen (regression of drusen faster and to greater degree with treatment, compared to controls); severe vision loss  —  treatment made no difference in 6-yr risk, com­pared to controls; late manifestations of AMD  —treatment did not affect risk for CNV or geographic atrophy (GA), compared to controls; conclusion  —  prophylactic laser treatment showed no long-term clinical benefit

More lessons learned from CAPT

Characteristics of CNV (Maguire et al, 2008): 68% of cases occult (one-third classic); 54% subfoveal (»50% extra­foveal); 56% small (£2 Macular Photocoagulation Study [MPS] disc areas); VA 20/40 or better in 70% of eyes; even if lesions subfoveal, 90% to 95% of eyes stabilized using anti-VEGF therapy (eg, ranibizumab); 25% of pa­tients developed CNV in both eyes; AREDS vitamin protocol indicated for nonsmokers; with close monitoring, »50% of CNV lesions detected outside fovea and when still relatively small; early detection and treatment may lead to improved long-term VA (better to treat at 20/40 than at 20/200)

Indications for close monitoring as suggested by inclusion criteria for CAPT: presence of bilateral large drusen (10 drusen ³125 mm), VA 20/40 in each eye, age ³50 yr

Risk factors (summary): for CNV  —  with older age risk increased 3-fold (relative risk [RR] 3); smokers (2-fold); fo­cal hyperpigmentation (2-fold); for GA  —  older age (risk increased 6-fold); greater drusen area (5-fold); retinal pigment epithelium depigmentation (RR 2.6); focal hyperpigmentation (RR 10)

Night vision symptoms: at baseline, participants given 10-item questionnaire related to night vision; findings corre­lated with risk for CNV, GA, or 3-line loss in VA (questionnaire reliably predicted which patients more likely to have these problems); for score in 4th quartile, RR for complications described 2 to 3, compared to 1st quartile

Conclusions: laser treatment not beneficial long-term; CAPT data support close follow-up of patients with bilateral large drusen; CNV often treatable, especially if extrafoveal, small, and in patients with good VA; night vision com­plaints worrisome

Suggested Reading

Complications of Age-Related Macular Degeneration Prevention Trial Research Group: Laser treatment in patients with bilat­eral large drusen: the complications of age-related macular degeneration prevention trial. Ophthalmology 113:1974, 2006; Chew EY et al: Risk of advanced age-related macular degeneration after cataract surgery in the Age-Related Eye Disease Study: AREDS report 25. Ophthalmology 116:297, 2009; Diabetic Retinopathy Clinical Research Network: A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology 115:1447, 2008; Frennesson CI: Prophylactic laser treatment in early age-related maculopathy: an 8-year follow-up in a randomized pilot study shows a reduced incidence of exudative complications. Acta Ophthalmol Scand 81:427, 2003; Friberg TR et al: Prophylactic treatment of age-related macular degeneration report number 1: 810-nanometer laser to eyes with drusen. Unilaterally eligible patients. Ophthalmology 113:622, 2006; Kaiser RS et al: Laser burn intensity and the risk for choroidal neovascularization in CNVPT Fellow Eye Study. Arch Ophthalmol 119:826, 2001; Lanchoney MD et al: A model of the incidence and consequences of choroidal neovascularization sec­ondary to age-related macular degeneration. Comparative effects of current treatment and potential prophylaxis on visual outcomes in high-risk patients. Arch Ophthalmol 116:1045, 1998; Little HL et al: A pilot randomized controlled study on the effect of laser pho­tocoagulation of confluent soft macular drusen. Ophthalmology 105:760, 1998; Maguire MG et al: Characteristics of choroidal neo­vascularization in the complications of age-related macular degeneration prevention trial. Ophthalmology 115:1468, 2008; Olk RL et al: Therapeutic benefits of infrared (810-nm) diode laser macular grid photocoagulation in prophylactic treatment of nonexudative age-related macular degeneration: two-year results of a randomized pilot study. Ophthalmology 106:2082, 1999; Owens SL et al: Prophylactic laser treatment appears to promote choroidal neovascularization in high-risk ARM: results of an interim analysis. Eye 17:263, 2003; Scorolli L et al: Argon laser vs subthreshold infrared (810-nm) diode laser macular grid photocoagulation in nonexu­dative age-related macular degeneration. Can J Ophthalmol 38:489, 2003; Yilmaz T et al: Intravitreal triamcinolone acetonide injec­tion for treatment of refractory diabetic macular edema: a systematic review. Ophthalmology 116:902, 2009.