In Part 3 of the Vit-Buckle Society’s Virtual Series, María H. Berrocal, MD, and Yasha S. Modi, MD, discussed the pros and cons of early vitrectomy versus medical therapy for patients with high-risk proliferative diabetic retinopathy (PDR). Dr. Berrocal outlined the advantages of early vitrectomy in patients with PDR, including lifting the hyaloid, which can act as a scaffold for neovascularization and traction. Dr. Modi discussed why a more conservative approach combining panretinal photocoagulation (PRP) and anti-VEGF therapy may pose less risk to the patient and potentially be just as efficacious.

Avni P. Finn, MD, MBA: Dr. Berrocal, what is your initial treatment for a patient with high-risk PDR?

María H. Berrocal, MD: I choose my initial treatment depending on whether the posterior hyaloid is completely detached or not. If there is a complete posterior vitreous detachment (PVD) and macular edema, I begin with anti-VEGF injections and add PRP later. If there is a complete PVD and no macular edema, I treat the patient with PRP up to 2 to 3 disc diameters (DD) from the arcades. If the hyaloid is not completely detached, particularly if there is vitreous hemorrhage or areas with fibrovascular proliferation, I usually offer vitrectomy. I explain the risk of progression with occurrence of tractional retinal detachment (TRD) and the benefits of long-term stabilization after vitrectomy with hyaloid removal. If the patient does not want surgery and has no diabetic macular edema (DME), I perform PRP as above. If the patient has associated DME, I start PRP inferiorly and concomitant anti-VEGF therapy and complete the PRP in two to three sessions. Subsequently, I treat the edema with anti-VEGF therapy, stressing the importance of compliance with appointments.

Basil K. Williams Jr, MD: What about you, Dr. Modi?

Yasha S. Modi, MD: My initial approach is combination anti-VEGF therapy and PRP, but even more important is the initial discussion with the patient regarding the severity of the disease, the likelihood of blindness in the absence of treatment, and the importance of regular follow-up to prevent severe complications. All first-visit patients in my clinic must agree and “sign” a verbal contract with me. I state, “I promise I will do everything possible to make sure you see for the rest of your life. However, you must promise me you will never miss an appointment with me or your primary care doctor or endocrinologist.”  This small act of verbal commitment combined with tracking of patients through the electronic health record system has lowered my rate of loss to follow-up, which is where devastating ocular complications may occur.

 When opting for combination PRP and anti-VEGF therapy over surgery, it’s important to realize that this is my framework that I apply across the majority of my patients but not necessarily all patients. As clinicians, we have to gauge the likelihood of disease progression with the implemented therapy with a readiness to pivot to surgery if the disease were to worsen (eg, progressive contraction of fibrovascular membranes with worsening traction). We must also gauge the likelihood of the patient’s compliance with return visits.

Dr. Finn: Dr. Berrocal, when do you consider early PPV for PDR?

Dr. Berrocal: I consider early vitrectomy in the following scenarios: eyes with attached hyaloid, severe disease with vitreous hemorrhage or areas of fibrosis, fibrovascular fronds, or TRD; patients who are poorly controlled or have concomitant renal involvement and hypertension; and patients who exhibit poor compliance or are at risk of losing insurance. If it is the patient’s first visit, I perform a fluorescein angiogram to show the pathology, talk about surgery, give the patient educational pamphlets, and start PRP in the periphery. The patient returns in 2 to 4 weeks to continue the conversation. Eyes with the above characteristics can quickly progress to TRD despite PRP (Figure).

Dr. Williams: Dr. Modi, what research guides your decision of whether to start with anti-VEGF therapy and PRP?

Dr. Modi: What makes high-risk PDR management so difficult is that we lack high-quality randomized clinical trials to guide decision-making. The DRCR Retina Network’s Protocol S was a landmark study that evaluated the initial treatment strategy for PDR with anti-VEGF therapy or PRP (with rescue anti-VEGF for DME).1 However, only 1% of patients enrolled in that protocol had high-risk PDR with a diabetic retinopathy severity score of 85 (presence of preretinal or vitreous hemorrhage at presentation) or worse.

Thus, when we encounter patients with high-risk PDR, we must turn our attention to another well-executed multicenter randomized clinical trial called the PROTEUS study, which evaluated combination PRP plus anti-VEGF therapy versus PRP alone for initial management of high-risk PDR.2 Regression of neovascularization at 1 year was seen in 93% of patients receiving combination PRP and anti-VEGF therapy, compared with 71% of those receiving PRP alone. Progression to surgery was seen in 2.5% of patients in the combination group and 11% in the PRP group, indicating three things:

  1. A combination approach is superior to PRP alone;
  2. the vast majority of patients managed initially with conservative measures did well; and
  3. a small percentage of patients will still require surgery despite intensive PRP and anti-VEGF therapy.

These data provide me a reasonable framework to start with initial therapy of combination PRP with anti-VEGF therapy for these high-risk patients.

Dr. Finn: Dr. Berrocal, you presented some strong evidence for early vitrectomy with your own case series of 60 patients who had PPV in one eye and PRP in the other eye. In these patients, 8% of eyes that had PPV ended up with hand motions (HM) or worse VA, whereas 36% of eyes treated with PRP had HM or worse VA. Similarly, series of patients treated with anti-VEGF therapy alone often show that lapses in follow-up due to illness, financial hardship, or noncompliance lead to poorer outcomes.3,4 Can you elaborate on what you see as the advantages of early PPV for PDR?

Dr. Berrocal: The advantages of early vitrectomy in PDR are most notable in eyes with a totally or partially attached hyaloid. Detaching the hyaloid during surgery removes the scaffold for neovascularization and prevents TRD or combined rhegmatogenous and TRD, as well as reducing the risk of macular edema, macular hole, and vitreomacular traction. With early vitrectomy we avoid the main complications of PDR that cause visual loss, reduce the need for many follow-up visits, and stabilize the eyes long-term. During the procedure, I always do PRP to the ora and up to 2 to 3 DD from the arcades. In young patients, the risk of cataract progression is small, and the procedure is essentially curative. With advances in vitrectomy, early PPV is a relatively simple procedure with minimal complications, and it is cost-effective to the patient and society. The advantages of stable visual acuity and reduction of the number of physician visits, time, and monetary costs are immense for individuals with diabetes.  

Dr. Williams: Dr. Modi, what do you see as the drawbacks or potential risks of early PPV for PDR?

Dr. Modi: There is nothing better than beautifully executed diabetic surgery with total posterior hyaloid delamination that renders the patient stable in perpetuity. This is the goal for all surgeries, and we are fortunate as retina specialists to execute to this standard in the majority of cases given recent technological advancements. However, some potential drawbacks occur when even small complications such as a retinal break balloon to proliferative vitreoretinopathy superimposed on PDR. One study reported retinal breaks in diabetic surgery in 4% of patients receiving 23-gauge PPV.5 Additionally, in cases in which the surgeon may not be able to achieve full delamination or when segmentation is incomplete, reoperation rates may be unacceptably high.

Finally, each surgical case poses interesting technical challenges, and each surgeon has unique skills and limitations. Thus, it is incumbent on each retinal surgeon to appraise each situation and calculate his or her own risk when considering surgical intervention as the first-line approach. 

1. Gross JG, Glassman AR, Liu D, et al; Diabetic Retinopathy Clinical Research Network. Five-year outcomes of panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA Ophthalmol. 2018;136(10):1138-1148.

2. Figueira J, Fletcher E, Massin P, et al; Study Group. Ranibizumab plus panretinal photocoagulation versus panretinal photocoagulation alone for high-risk proliferative diabetic retinopathy (PROTEUS study). Ophthalmology. 2018;125(5):691-700.

3. Wubben TJ, Johnson MW; Anti-VEGF Treatment Interruption Study Group. Anti-vascular endothelial growth factor therapy for diabetic retinopathy: consequences of inadvertent treatment interruptions. Am J Ophthalmol. 2019;204:13-18.

4. Obeid A, Su D, Patel SN, et al. Outcomes of eyes lost to follow-up with proliferative diabetic retinopathy that received panretinal photocoagulation versus intravitreal anti-vascular endothelial growth factor. Ophthalmology. 2019;126(3):407-413.

5. Choovuthayakorn J, Khunsongkiet P, Patikulsila D, et al. Characteristics and outcomes of pars plana vitrectomy for proliferative diabetic retinopathy patients in a limited resource tertiary center over an eight-year period. J Ophthalmol. 2019;2019:9481902.