DIABETIC RETINOPATHY
| DIABETIC RETINOPATHY DIAGNOSIS AND TREATMENT —Juan Orellana, MD, Clinical Associate Professor,
University of North Carolina School of Medicine, Chapel Hill
|
| Incidence: in United States, diabetic maculopathy one of leading causes of new cases of legal blindness in patients 24 to
74 yr of age; 86% of patients with type 1 diabetes have retinopathy (42% have sight-threatening retinopathy); incidence
varies widely among ethnic groups; diabetes and retinopathy increase as geriatric population increases; diabetic
macular edema (DME)—most common cause of visual loss in diabetic patients; affects almost half of type 1 diabetics;
25% have substantial visual loss after ≈3 yr; 50% of patients lose >2 lines of visual acuity within 2 yr
|
| Background diabetic retinopathy (BDR): microaneurysms; intraretinal hemorrhages; cotton wool spots (nerve fiber
layer infarcts); intraretinal microvascular abnormalities
|
| Clinically significant macular edema (CSME): components—thickening of retina within 500 µ of macular center;
hard exudate at or within 500 µ of center; retinal thickening greater than disc area; thickening within disc diameter of
macular center; Early Treatment Diabetic Retinopathy Study (ETDRS)—gold standard; focal/grid laser photocoagulation
for CSME cuts moderate vision loss by ≈50%; probably more helpful for focal treatment than for diffuse edema;
optical coherence tomography (OCT)—hemorrhages, blood vessels, and vascularity project into scan; able to distinguish
edema associated with vitreoretinal traction or adhesions; small epiretinal membrane may lift edge of macula
and cause edema; shallow macular detachments best seen on OCT; case—cotton wool spots; edema; cystic spaces
typically seen in patients with DME; at 500 µ from fovea, retinal thickness 175 µ to 200 µ (rarely >215 µ); DME
types—spongelike retinal swelling; cystoid macular edema (CME); serous retinal detachment
|
| Direct modulators: anti-vascular endothelial growth factor (VEGF) proteins—may prevent blood flow abnormalities;
protein kinase C (PKC) inhibitors—help regulate endothelial permeability, blood flow, and angiogenesis; increased
levels promote leukocyte-endothelial cell adhesions and capillary occlusion
|
| Indirect modulators: somatostatin—growth hormone; blunts rise of VEGF; cyclooxygenase (COX)-2 inhibitors—
cyclooxygenase causes angiogenesis through prostanoids (increase VEGF); studies looking at pegaptanib (Macugen)
for prevention of neovascularization due to diabetes; angiotensin-converting enzyme (ACE) inhibitors—in rat
model, lisinopril reduces angiogenesis in retinopathy of prematurity (ROP); antioxidants—inhibition of superoxide
can block sorbitol accumulation
|
 | Oral agents: ruboxistaurin—PKC inhibitor; in randomized clinical trial, significant reversal of blood flow abnormalities;
inflammatory component—some physicians have tried using prednisolone (Pred Forte); speaker has used triamcinolone
(Kenalog) and ketorolac (Acular) for early DME; newer nonsteroidal anti-inflammatory drugs (NSAIDs)—
nepafenac (Nevenac); bromfenac (Xibrom)
|
| Focal laser: works well for localized edema (for diffuse edema, less powerful); diffuse grid laser may be effective
(≈25% of patients still lose >3 lines)
|
| Activity: measurable levels sustained 3 mo (worry is glaucoma); decrease in VEGF; inhibition of metabolism of
arachidonic acid (prostaglandin by-product); VEGF and prostaglandin contribute to edema
|
| Technique: take care not to inject air into bottles; apply 2% lidocaine (Xylocaine) swab so that patient does not feel injection
of Kenalog subconjunctivally; add antibiotics
|
| Optimal dose (study): 4-mg and 25-mg doses worked well (greater incidence of glaucoma at 25 mg); on OCT, gradual retinal
thinning over 6 mo; adverse effects—intraocular pressure (IOP) increase (treat with topical medication); if immediate,
tap anterior chamber (AC) with 27- or 30-gauge needle (problem occurs up to 3 mo later in ≈25% of patients)
|
| Intravitreal injection (study by Massin): marked retinal thinning; increased IOP in 50% of patients; better visual acuity
in 5 of 12 patients
|
| Complications of Kenalog injection: cataract; ocular hypertension or glaucoma; endophthalmitis
|
| Subconjunctival hemorrhage: occurs in 9 of 10 patients injected intravitreally; epinephrine too risky in diabetic patient
(instead, educate patient)
|
| Infectious endophthalmitis: incidence varies up to 1%; most common pathogens Staphylococcus and Streptococcus;
clinical presentation—varied; AC reaction; vitreous haze; pain; decreased vision; pseudohypopyon; or none
|
| More about Kenalog technique: topical moxifloxacin (Vigamox) or gatifloxacin (Zymar) q 5 min to 4 doses; rinse conjunctiva
with sodium acetate (balanced salt solution [BSS]); consider administering 2% Xylocaine subconjunctivally
at 6 o’clock position; inject 0.1 mL Kenalog; if needed, AC tap; additional antibiotics (3 doses); sterile procedure—
topical antibiotics important; alcohol to bottle tops; refrain from injecting air into bottles; speaker does not use povidone
iodine (Betadine; some reports of endophthalmitis); careful tap of AC
|
| Vitrectomy: goal to decrease traction that leads to vascular hyperpermeability; technique—typically, standard 3-point
vitrectomy; internal limiting membrane (ILM) peel; procedure may increase nuclear sclerosis
|
| PROLIFERATIVE DIABETIC RETINOPATHY: TREATMENT —Dr. Orellana
|
| Diagnosing proliferative diabetic retinopathy (PDR): patient diagnosed in past as “borderline diabetic” may present
with florid disc neovascularization; vitreous hemorrhage key in vision loss (large hemorrhages mean neovascularization);
subhyaloid hemorrhage; traction retinal detachments (some reattach spontaneously) and possible breaks; vitreous
hemorrhage—some cleared with hyaluronidase (Vitrase), then treated with laser
|
| Efficacy of laser (Diabetic Retinopathy Study [DRS]): at 3 yr, treatment better than no treatment; argon laser treatment
as effective as xenon (xenon laser gives large primitive burn); speaker uses xenon laser treatment in patients with persistent
neovascular vessels (despite argon laser therapy) and patients with medium-sized melanomas; visual acuity at least
5/200 achieved in 8% of xenon-treated eyes (13% of argon-treated eyes; 26% of nontreated eyes); panretinal photocoagulation
(PRP) beneficial, but does not guarantee preservation of vision
|
| Panretinal photocoagulation
|
| Rate of regression of neovascularization of disc (NVD): total regression (only 30%); mild neovascularization (almost
41%); partial regression (27%); in untreated eyes with mild NVD, 13% had total regression (13%, partial)
|
| Benefits: early treatment more likely to preserve visual acuity than PRP when NVD advanced and may abort fibrovascular
proliferation (decreases incidence of traction retinal detachments); patients with preproliferative disease who
receive PRP may avoid NVD and neovascularization of new vessels elsewhere
|
| Retinopathy risk-factor regression after laser PRP for PDR (Doft and Blankenship): best prognosis if some regression
at 3 wk; 50% of patients have total regression by 6 mo (stable in about one third); if no regression at 3 wk, only 36%
show no NVD at 6 mo
|
| Mechanism of success: limits portion of retina that requires oxygen; maximum damage by PRP in outer retinal layers
(decreasing numbers help remaining cells survive); reduction of vasoproliferative factor by hypoxic retina
|
| Adverse effects: diminution of visual field; color desaturation; decreased night vision
|
| Cryoretinopexy: helpful if media cloudy; influx of macrophages into vitreous cavity helps clear vitreous hemorrhage;
may exacerbate traction by causing breaks or retinal detachment; complications—increased IOP; inflammation; iritis,
iris atrophy; fixed and dilated pupil; transient loss of accommodation (if treatment extends to ciliary nerves); cataract
formation; CME; epiretinal membrane; retinal tears or detachment; vitreous, retinal, or suprachoroidal hemorrhages
|
| Vitrectomy: indications—vitreous hemorrhage and visual loss; traction retinal detachments; PRP has not achieved regression
of neovascularization; persistent neovascular tissue despite extensive PRP or cryoretinopexy; caveat (small
hemorrhage may clear with time); Vitrase as treatment for vitreous hemorrhage (off-label use)—in recent study,
treatment caused low-grade uveitis next day; treatment worked well, but some end points of study muddled; may play
role in patients with vitreous hemorrhage for 1 to 3 mo who do not have access to vitrectomy; indications for vitrectomy
revisited—neovascular tissue identified; adequate PRP (3000-3500 spots); xenon laser or cryoretinopexy previously
considered; vitreous turbid from hemorrhage; traction where retina tented; hemorrhage precludes more laser therapy; retinal
detachment; standard procedure—removal of posterior hyaloid; in speaker’s experience, ILM peel not necessary;
additional laser or cryoretinopexy can be added; if residual bleeding, consider gas or air to achieve hemostasis after adequate
laser therapy; be certain that scaffolding removed so that new blood vessels do not grow into scar tissue and cause
rebleeding; on occasion, surviving vessels well established and difficult to ablate (direct cautery may be indicated); persistent
disc neovascularization responds favorably to vitrectomy; more issues—diabetic vitrectomy sometimes >1 procedure;
quality of acuity after vitrectomy; likelihood of adherence to follow-up care; smoking another mechanism by
which vasculature attenuated
|
| PREOPERATIVE PLANNING: CATARACT SURGERY IN THE DIABETIC PATIENT —Susanna S. Park, MD, Associate
Professor of Ophthalmology, University of California, Davis, School of Medicine
|
| Diabetes and cataract (overview): incidence of cataract in patient with diabetes 2 to 4 times more common than general
population; leading cause of vision loss (not diabetic retinopathy); in diabetic patient, cataract has earlier age of onset;
incidence of cataract surgery within 10 yr if <45 yr of age, 27% (<75 yr of age, 44%)
|
| Cataract surgery risks for diabetic patient: concurrent diabetic retinopathy; progression of retinopathy; CME; corneal
edema; posterior capsular opacity; fibrinous uveitis
|
| Unresolved issues: appropriate timing of surgery; determination of visual outcome; effect of surgery on retinopathy; optimal
preoperative management to minimize risk of worsening diabetic retinopathy
|
ETDRS Report #25
| Prognostic comparison of diabetic patients
|
| No retinopathy: excellent visual outcomes after cataract surgery; rate of success comparable to nondiabetic patient; in
recent study, 93% of patients 20/40 or better after surgery
|
| With retinopathy (study): >3000 patients randomized to early or delayed PRP; 270 patients underwent cataract surgery;
visual outcome after cataract surgery correlated with severity of preoperative retinopathy; visual improvement
≥2 lines with cataract extraction (CE)—overall incidence 62%; in 15% of patients, visual outcome >2 lines worse
than preoperative vision; for severe nonproliferative diabetic retinopathy (NPDR) or PDR, incidence of visual improvement
55%; visual acuity 1 yr after CE—of patients with severe NPDR or PDR, only 25% 20/40 or better
(many had macular edema [ME], vitreous hemorrhage, or traction retinal detachment); mild-to-moderate NPDR
(53% 20/40 or better)
|
| Early vs deferred laser treatment: early treatment (PRP) for PDR or ME associated with better outcome than deferred
treatment; visual acuity improvement ≥2 lines with CE—with early PRP, rate 64%; deferred laser group (59%); visual
acuity 1 yr after CE—early laser (46% 20/40 or better); deferred laser (36%)
|
| Risk for progression of retinopathy (study): progression defined as 2-step advancement in retinopathy (ie, progression
from mild NPDR to severe NPDR or PDR); trend toward retinopathy progression (P = 0.03 for 2-step progression)
|
| Risk for ME (study): incidence before and after CE almost same (no significant difference); but some patients had preoperative
or postoperative focal laser; in addition, study conducted before OCT able to quantitate severity of ME; preoperative
ME with retinal exudate associated with poorer postoperative visual acuity
|
| Natural history of DME after CE (study by Dowler): 32 patients with diabetic retinopathy but no high-risk characteristics;
fluorescein angiography before surgery and 3, 6, 9, and 12 mo postoperatively; 94% of patients developed ME after
surgery (however, 43% had full resolution of leakage by 1 yr); if ME present preoperatively, no eyes recovered
spontaneously; study excluded patients with CSME preoperatively; 56% incidence of CSME postoperatively (of
those, 50% spontaneously resolved at 6 mo; 75% at 1 yr); if CSME present at time of surgery, resolution unlikely; if
retinopathy severe, resolution also unlikely
|
| Risk factors for poor visual outcome after CE: poor preoperative visual acuity; severity of retinopathy; macular ischemia;
CSME; risk for ME progression if present at time of surgery; concurrent maculopathy (eg, macular degeneration,
retinal detachment, or epiretinal membrane)
|
| Preoperative planning: detailed dilated fundus examination just before surgery and within 2 wk to rule out progression
of retinopathy; treat any retinal neovascularization or ME early; wait for complete regression of retinal neovascularization
and ME before clearing patient for cataract surgery; inform patient of risk for poor visual outcome due to diabetes
|
Educational Objectives
| The goal of this program is to educate the listener about diagnosis and management of diabetic retinopathy. After hearing
and assimilating this program, the clinician will be better able to:
|
| 1. Diagnose clinically significant diabetic retinopathy.
|
| 2. Describe newer medical treatments for managing diabetic macular edema.
|
| 3. Minimize the risk for complications associated with intraocular triamcinolone (Kenalog).
|
| 4. Describe strategies for managing proliferative diabetic retinopathy.
|
| 5. Recognize special preoperative considerations in diabetic patients who are candidates for cataract surgery.
|
Discussed on This Program
Bromfenac 0.09% ophthalmic solution (Xibrom)
Gatifloxacin [Tequin, Zymar]
Hyaluronidase [Vitrase, Amphadase]
Ketorolac tromethamine [Acular]
Lidocaine HCl (several formulations and trade names)
Moxifloxacin HCl [Avelox, Avelox I.V., Vigamox]
Nepafenac ophthalmic suspension 0.1% (Nevanac)
Pegaptanib sodium [Macugen]
Povidone iodine (several formulations and trade names)
Prednisolone [PredForte, others]
Ruboxistaurin (investigational)
Sodium acetate [AMO Endosol, Balanced Salt Solution, BSS, Iocare Balanced Salt]
Triamcinolone acetonide [Kenalog, others]
Suggested Reading
Browning DJ: Visual dysfunction after panretinal photocoagulation in patients with severe diabetic retinopathy and
good vision. Am J Ophthalmol 140:127, 2005; Chew EY et al: Results after lens extraction in patients with diabetic retinopathy:
early treatment diabetic retinopathy study report number 25. Arch Ophthalmol 117:1600, 1999; Chew EY et
al: The long-term effects of laser photocoagulation treatment in patients with diabetic retinopathy: the early treatment diabetic
retinopathy follow-up study. Ophthalmology 110:1683, 2003; Davis MD et al: Risk factors for high-risk proliferative
diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18. Invest
Ophthalmol Vis Sci 39:233, 1998; Doft BH, Blankenship G: Retinopathy risk factor regression after laser panretinal
photocoagulation for proliferative diabetic retinopathy. Ophthalmology 91:1453, 1984; Dowler JG et al: The natural
history of macular edema after cataract surgery in diabetes. Ophthalmology 106:663, 1999; Massin P: Intravitreal triamcinolone
acetonide for diabetic diffuse macular edema: preliminary results of a prospective controlled trial. Ophthalmology
111:218, 2004; Mozaffarieh M et al: Photocoagulation for diabetic retinopathy: determinants of patient satisfaction
and the patient-provider relationship. Acta Ophthalmol Scand 83:316, 2005; Shimura M et al: Visual dysfunction after
panretinal photocoagulation in patients with severe diabetic retinopathy and good vision. Am J Ophthalmol 140:8, 2005;
Soto-Pedre E et al: Risk factors for postoperative hemorrhage after vitrectomy for diabetic retinopathy. Ophthalmic Epidemiol
12:335, 2005; The PKC-DRS Study Group: The effect of ruboxistaurin on visual loss in patients with moderately
severe to very severe nonproliferative diabetic retinopathy: initial results of the Protein Kinase C beta Inhibitor
Diabetic Retinopathy Study (PKC-DRS) multicenter randomized clinical trial. Diabetes 54:2188, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. Dr. Orellana has received
research grants from Alcon, Allergan, Ista Pharmaceuticals, and Lilly Roche.
Dr. Orellana was recorded at the 4th Annual Downeast Ophthalmology Symposium, Practical Solutions in Ophthalmology
, presented September 23-25, 2005, in Bar Harbor, Maine, by the Maine Society of Eye Physicians and Surgeons;
Dr. Park was recorded at the 28th Annual UC Davis Ophthalmology Symposium, Cataract Surgery From A to Z (And
Beyond), presented May 13-14, 2005, in Sonoma, California, by the University of California, Davis, Health System, Department
of Ophthalmology and Vision Science, and Continuing Medical Education. The Audio-Digest Foundation
thanks Drs. Orellana and Park and the sponsors for their cooperation in the production of this program.
|
