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Point–Counterpoint


Is Prophylactic PRP in Ischemic CRVO a Good Idea?



Yes, It’s Worth It in Some Cases

No, It May Do More Harm than Good



Yes, It’s Worth It in Some Cases

A cost-utility analysis of prophylactic PRP for ischemic CRVO reveals that the clinical trial’s results may only be half of the picture.

Gary Brown, MD, MBA, Melissa Brown, MD, MN, MBA,
Philadelphia

Though clinical trials are good for determining efficacy, they’re only half the story. The rest is composed of how well the treatments work in practice and whether the benefits outweigh the cost. Though the Central Retinal Vein Occlusion Study determined that prophylactic laser for ischemic CRVO eyes held no benefit, when the study’s data is analyzed using a method called cost-utility analysis, which incorporates both photocoagulation’s (PRP) efficacy and patient quality of life, prophylactic PRP is actually beneficial for certain patients. Here’s why.

Evidence-Based Medicine and Value
As far as interventional evidence-based medicine goes, the Central Vein Occlusion Study, as de-signed, is an example of the highest level of quality.1 However, just as important as the evidence-based data is the value of the data to patients.

Cost-utility analysis allows us to measure the value of healthcare interventions. The methodology incorporates the patient-perceived quality of life using a continuum of utility values in which 0.0 is the worst (death) and 1.0 is the best (perfect health).2,3,4

In addition to incorporating the improvement in quality of life from an intervention, cost-utility analysis also incorporates any improvement in lifespan and the costs associated with an intervention to determine the value.4-13 To this end, cost-utility analysis is composed of three elements: utility values, the length of time the patient can enjoy the benefits and the cost.

Though utility values are helpful in understanding how a treatment im-proves the quality of life, they don’t describe the duration of the quality or the increase in lifespan. To do this, researchers have devised the idea of quality-adjusted life-years (QALYs). To determine the QALYs gained by a treatment, you multiply the gain in utility by the duration of the change. For example, if a patient were to gain 0.3 utility points after cataract surgery for 20 years of his life, he would have a net gain of 0.3 x 20=6.0 QALYs. In cases with a recurrent risk of an adverse event, a mathematical technique known as Markov Modeling may be necessary. Basically, this determines the probability of an event’s occurring.

Next, cost is introduced to complete the equation. This consists of dividing the cost of the therapy by the QALYs, or $/QALY. While the criteria vary from one society to another, it has been suggested that interventions costing less than $20,000/QALY gained are cost-effective, while those costing greater than $100,000/QALY gained are not.14

From this cost-utility standpoint, prophylactic PRP for certain cases of ischemic CRVO makes a lot of sense.

In our calculations, the assumptions for ischemic CRVO are based upon data from the literature. It should be noted that the assumptions in our model herein are weighted toward an approach favoring observation. They include:

• Clinical Assumptions
  1. Thirty-five percent of untreated ischemic CRVO (>10 disc areas of capillary nonperfusion) eyes develop iris neovascularization (NVI).1
  2. Half of very ischemic CRVO eyes (>75 disc areas of nonperfusion and/or vision less than 20/800) develop NVI.1,15
  3. Twenty percent of ischemic CRVO eyes treated with prophylactic PRP develop NVI.15
  4. Visual acuity results are converted to utility values for the decision analysis tree (See Figure 1).4
  5. Nine to 81 percent of eyes with iris neovascularization develop neovascular glaucoma, which has a poor outcome (final visual acuity of worse than hand motions and the necessity of additional therapy such as cyclocyotherapy).15,16


• Economic Assumptions
  1. The incremental costs of prophylactic therapy for ischemic CRVO include: $853 (CPT procedure #67228) x (1.0 - proportion of treated eyes developing NVI).17
  2. A straight decision-analysis tree was employed with utility value calculations at the time of the initial examination (See Figure 1).
  3. Eyes with a poor visual outcome secondary to neovascular glaucoma require cryoablation of the ciliary body (CPT #66720, cost = $421).17
  4. Eyes that don’t undergo PRP incur the additional cost of two office visits (each with CPT #92012 @ $53, for a total cost of $106).
  5. We used Markov Modeling to account for the recurrent annual risk of 0.9 percent of developing a retinal vascular obstruction in the fellow eye.


Results of the Cost-Utility Analysis
  • All ischemic eyes. This group is composed of eyes with greater than 10 disc areas of capillary nonperfusion.1 In it, 35 percent develop NVI without early PRP and 20 percent develop NVI with early PRP. If 9 percent of eyes that develop neovascular glaucoma have a poor outcome (acuity worse than hand motions), the $/QALY gained from laser PRP prior to the NVI is $175,840.15 If 81 percent of eyes that develop neovascular glaucoma have this outcome, the $/QALY gained from laser PRP prior to the development of NVI is $21,498.16
  • Very ischemic eyes. These eyes are defined as having greater than 75 disc areas of nonperfusion or vision worse than 20/800, in which half develop NVI without early PRP and 20 percent develop NVI with early PRP. If 9 percent of eyes that develop neovascular glaucoma have a poor outcome (acuity worse than hand motions) the $/QALY gained from prophylactic PRP prior to the NVI is $16,036.1 If 81 percent of eyes that develop neovascular glaucoma have a poor outcome, the $/QALY gained is $4,185.16


It appears, analyzing the above data, that treating eyes with a very ischemic CRVO prior to iris neovascularization is a cost-effective procedure. Thus, the clinician has reasonable evidence-based data to support early treatment if there is greater than 75 disc areas of fluorescein angiographic nonperfusion or if the vision drops to less than 20/800.

For the assumption that 81 percent of eyes that develop iris neovascularization progress to neovasular glaucoma and a poor outcome, the $/QALY is borderline—$21,498.16 The actual chance of iris neovascularization leading to severe neovascular glaucoma and a poor visual outcome probably lies somewhere between the 9-percent incidence noted in patients followed closely in a clinical trial and the 81-percent incidence observed in a busy clinic in which follow-up isn’t as closely measured.

A major reason laser therapy for very ischemic CRVO is cost-effective is because it appears to prevent the deterioration of vision in a subset of eyes with iris neovascularization and neovascular glaucoma from counting fingers to hand motions. The benefit of the intervention becomes apparent when this degree of visual loss occurs in both eyes, as occurs in 9 percent of patients when first seen, and an additional 0.9 percent of the remaining cohort per year. With the occurrence of bilaterality, the quality of life diminishes dramatically.4

Ultimately, clinical trials can tell us whether a treatment is effective and relatively safe. However, when thrust into the arena of medical practice, in which we have to juggle such priorities as a patient’s quality of life and procedural costs, raw clinical data fall short. In ischemic CRVO, when such variables are accounted for, prophylactic PRP shows that it has some value after all. 

Dr. Gary Brown is professor of ophthalmology at Jefferson Medical College and is director of the Retina Vascular Unit at Wills Eye Hospital. Dr. Melissa Brown is an assistant surgeon at Wills Eye. Both are directors of the Center for Evidence-based Healthcare Economics, Flourtown, Pa.

  1. The Central Retinal Vein Occlusion Study Group. A randomized clinical trial of early panretinal photocoagulation for ischemic central retinal vein occlusion. The Central Vein Occlusion Study Group N Report. Ophthalmology 1995;102:1434-1444.
  2. Brown MM, Brown GC, Sharma S, Shah G. Utility values and diabetic retinopathy. Am J Ophthalmol 1999;128:324-330.
  3. Brown MM, Brown GC, Sharma S, Kistler J. Utility values associated with age-related macular degeneration. Arch Ophthalmol 2000;118:47-51.
  4. Brown GC. Vision and quality of life. Trans Am Ophthalmol Soc 1999;97:473-512.
  5. Brown GC, Sharma S, Brown MM, Garrett S. Evidence-based medicine and cost-effectiveness. J Healthcare Fin 1999;26:14-23.
  6. Brown MM, Brown GC, Sharma S, Garrett S. Evidence-based medicine, utilities, and quality of life. Curr Opin Ophthalmol 1999;10:221-226.
  7. Brown GC, Brown MM, Sharma S. Health care in the 21st century. Evidence-based medicine, patient preference-based quality and cost-effectiveness. Quality Management in Health Care (in press).
  8. Brown GC, Brown MM, Sharma S. Quality and cost-effectiveness in health care: A unique ap-proach. J Ophthalmic Nursing & Technology 2000; Jan-Feb:26-30.
  9. Brown MM, Brown GC, Sharma S. Cost-effective analysis. The value component of evidence-based medicine. Evidence-Based Eye Care 2000;1(4):243-247.
  10. Brown GC, Brown MM, Sharma S, Tasman W, Brown H. Cost-effectiveness of therapy for threshold retinopathy of prematurity. Pediatrics 1999;104(4):e47.
  11. Brown GC, Brown MM, Sharma S. Incremental cost-effectiveness of laser therapy for subfoveal choroidal neovascularization. Ophthalmology 2000;107:1374-1380.
  12. Smith A, Brown GC. Understanding cost-effectiveness: A detailed review. Br J Ophthalmol 2000;54:794-798.
  13. Brown MM. The greatest need in health care: Quality standards. Evidence-Based Eye Care 2000;1(2):69-71.
  14. Laupacis A. Feeny D, Detsky AS, Tugwell PX. How attractive does a new technology have to be to warrant adoption and utilization. Tentative guidelines for using clinical and economic evaluations. Can Med Assoc J 1992;146:473-481.
  15. The Central Retinal Vein Occlusion Study Group. Natural history and clinical management of central retinal vein occlusion. Arch Ophthalmology 1997;115:486-491.
  16. Magargal LE, Brown GC, Augsburger JA, Parrish RK. Neovascular glaucoma following central retinal vein obstruction. Ophthalmology 1981;88:1095-1101.
  17. Davis JB. Medical Fees in the United States. Nationwide Charges for Medicine, Surgery, Laboratory, Radiology and Allied Health Services. Los Angeles, Practice Management Information Corporation, 2000.

No, It May Do More Harm than Good

A randomized clinical trial found no benefit to prophylactic laser treatment, and that should guide our therapy, says this physician.

John Clarkson, MD
Miami

When we undertook a trial of early panretinal photocoagulation (PRP) for ischemic central retinal vein occlusion (CRVO), we weren’t sure what we’d find. At the outset, I and the other researchers of the Central Vein Occlusion Study Group thought it reasonable to expect preventive PRP would stop the growth of iris neovascularization before it even started. However, as is sometimes the case in studies, what seems reasonable often has to give way to what actually is.

As it turned out, the prophylactic laser treatment didn’t eliminate the development of rubeosis. In fact, we discovered that it may actually be detrimental in patients who go on to develop rubeosis. Here is an explanation of my stance, based primarily on the data from our randomized trial.

The study.
In the study, we randomly assigned 180 eyes of 181 pa-tients to either immediate prophylactic PRP (90 eyes) or to observation. The latter group only received PRP if neovascularization later developed. We followed the study’s patients for three years.

Overall, 18 (20 percent) of the early treatment eyes and 32 (35 percent) of the control group developed anterior segment neovascularization. Though this showed a trend toward fewer instances of neovascularization in prophylactically treated eyes, the trend wasn’t statistically significant.1

However, perhaps more significant than the fact that prophylactic laser didn’t have an impact on the development of anterior segment neovascularization was that it may have diminished the ef-fects of future therapy.

In the study, the anterior segment neovascularization was gone at one month in 18 (56 percent) of the 32 eyes in the group that didn’t receive early treatment, but in only 4 (22 percent) of the 18 eyes in the early treatment group. Overall, we found that regression of the anterior segment neovascularization was more than four times as likely in eyes without prophylactic treatment than in those with pretreatment.1 Also, most of the patients who didn’t undergo early treatment saw a resolution of the neovascularization within a month of the PRP for it. And around 90 percent of eyes in both groups eventually stabilized without any neovascularization.

These results are also significant because we save patients the necessity of having to return for treatment until it’s really necessary. This prophylactic treatment only results in wasting more time for the patient, since close follow-up is still necessary. This is be-cause, in the study, neovascularization developed in both pretreated and untreated eyes, yet it responded very well to PRP. There-fore, careful follow-up, at least monthly during the first six to eight months after diagnosis of ischemic CRVO, is crucial.

Avoiding unnecessary prophylactic laser may allow patients to enjoy more usable vision for a longer period.

We know that many CRVO patients lose central vision as a result of the condition. When you couple this with the fact that PRP can potentially cause the loss of peripheral vision, it makes prophylactic laser treatment more undesirable. By performing PRP prophylactically, then, we may be robbing patients of some of their remaining useful vision after the CRVO has run its course. If we wait to apply PRP until it’s necessary, however, patients can potentially retain more vision.

Cutting out the prophylactic-PRP step also avoids the possible complications associated with the laser treatment, however small the risk. These include retinal detachment, full thickness retinal burns, and the possible adverse events associated with the use of retrobulbar anesthetic.

Rather than being concerned about prophylaxis, we should instead focus on the quantification of risk factors for anterior segment neovascularization. In the CVOS, the strongest predictor of anterior segment neovascularization was the extent of the retinal nonperfusion. Other risk factors were large amounts of retinal hemorrhage, short duration of CRVO and male gender. Eyes with less than 30 disc diameters of nonperfusion and no other risk factor were only at low risk, while those with 75 disc diameters or more are at the greatest risk. It’s these that we should watch carefully.

Patients struck with ischemic CRVO deserve our best care. And though intuition may suggest that prophylactic PRP will help them, the results of a well-controlled, randomized clinical study say otherwise. 

Dr. Clarkson is dean of the medical school at the University of Miami. He served as chair of the Central Vein Occlusion Study Group.

  1. The Central Vein Occlusion Study Group. A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion. Ophthalmology 1995;102:1434-1444.

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