Diabetic retinopathy is an increasingly prevalent cause of vision loss in the United States. Up to 83% of people with type 1 and 40% of people with type 2 diabetes will develop diabetic retinopathy (DR). Of those, 42% with type 1 and 8% with type 2 diabetes will have vision-threatening disease. This makes DR the most common preventable cause of vision loss in the US working-age population.¹ Proliferative DR (PDR) may require surgical intervention with vitrectomy to improve vision or reduce the risk of vision loss in cases of vitreous hemorrhage or tractional RD.

With improvements in vitrectomy techniques expanding the indications, the overall rate of vitrectomies is increasing. A study of a managed-care network showed that from 2001 to 2012, the rate of vitrectomy for any indication increased 31%. However, perhaps due to better medical management and more nonsurgical treatment options, fewer vitrectomies are being performed for diabetics. During the same period the rate of vitrectomy among diabetics decreased 43%.² Despite this, vitrectomy remains a valuable tool in the treatment of diabetic eye disease.

In phakic patients, cataract is the most common complication after diabetic vitrectomy, with 57% of patients requiring cataract removal within 5 years and 71% within 10 years of vitrectomy.³ However, a frustrating cause of complication after diabetic vitrectomy continues to be persistent or recurrent vitreous hemorrhage. A case series from Wills Eye Hospital found that postoperative vitreous hemorrhage occurred after 32% of 23-gauge vitrectomies done for diabetic vitreous hemorrhage in 2013. Of these, 13% of eyes required reoperation. Risk factors for postoperative vitreous hemorrhage included incomplete panretinal photocoagulation (PRP) prior to vitrectomy, younger age, and phakia.⁴ It is worth noting that this modern rate of hemorrhage is much lower than the rate in early vitrectomy, which was as high as 68% in the first postoperative day.⁵ Another study found that other risk factors include intraoperative bleeding from neovascularization of the disk (odds ratio [OR] 3.395) and elevated HbA₁c (OR 1.403).⁶

CRYOTHERAPY

Different surgical techniques have been shown to decrease the risk of vitreous hemorrhage after diabetic vitrectomy. One study showed a 38% rate of vitreous hemorrhage with endolaser alone, 12% with endolaser plus anterior cryotherapy, and 4% with endolaser, anterior cryotherapy, and cryotherapy to the sclerotomy sites, respectively.⁷ The study showed decreasing rates of fibrovascular ingrowth at the sclerotomy sites with increasing intervention; these rates corresponded to decreasing rates of vitreous hemorrhage, suggesting that in most cases, vitreous hemorrhage is related to reactive changes at the sclerotomy sites. This suggests that one method to treat recurrent vitreous hemorrhage after diabetic vitrectomy may be peripheral retinal cryotherapy (eg, 2 rows of external cryopexy posterior to the ora serrata). In a different study looking at revision vitrectomy for recurrent vitreous hemorrhage after diabetic vitrectomy, 73% had no further hemorrhage after peripheral retinal cryotherapy and posterior-pole PRP.⁸ Of those that rebled after revision vitrectomy, half had known anterior hyaloidal neovascularization and the other half did not have a clear mechanism for the rebleeding.

FLUID-AIR EXCHANGE

Another option for postoperative vitreous hemorrhage is in-office fluid-air exchange. This can be accomplished by positioning the patient on his or her side with the eye to be treated in the dependent position. After retrobulbar or subconjunctival anesthesia, a lid speculum is placed and proper antiseptic preparation is applied, and a syringe with a 27-gauge needle is partially filled with air and inserted 3.5 mm posterior to the temporal limbus. Then small amounts of air are injected alternating with small amounts of vitreous fluid aspiration until a successful fluid-air exchange is completed. This has a success rate of 50% with a mean number of 1.5 exchanges required per patient in one series.⁹ Alternative methods, including a dual needle and syringe system (one for vitreous fluid aspiration and one for fluid injection) have also been described.¹⁰ The theoretical advantage of this method is greater stability for the vitreous cavity volume during the procedure due to coupling of the removal and injection volumes. To expedite the return of visual function, using tissue plasminogen activator (tPA) has been described with the dual-syringe system to break down and remove blood clots.¹¹

SMALL-GAUGE VITRECTOMY

Newer surgical technology may also help decrease the complication rates after diabetic vitrectomy. Microincisional vitrectomy describes a pars plana vitrectomy through sclerotomy ports that are 23, 25, or 27 gauge, compared to the traditional 20-gauge sclerotomy ports. Purported benefits are decreased incidence of retinal breaks and decreased need for suturing of the sclerotomy sites, which may lead to reduced local inflammation and thus less fibrotic and neovascular changes at sclerotomy sites. One study comparing 20-, 23-, and 25-gauge vitrectomy for severe DR found that the mircoincisional surgery had a decreased rate of neovascularization of the sclerotomy wounds (40% for 20 gauge, 0% for 23 gauge, and 13% for 25 gauge) without a notable difference in the incidence of postoperative hemorrhage (24% for 20 gauge, 29% for 23 gauge, and 18% for 25 gauge) or the need for revision vitrectomy for vitreous hemorrhage (9% for 20 gauge, 8% for 23 gauge, and 5% for 25 gauge).¹² Interestingly, in this study there was also a significantly decreased rate of neovascular glaucoma for the 25-gauge microincision group (11% for 20 gauge vs 8% for 23 gauge and 3% for 25 gauge groups).

The advent of microincision surgery, particularly 27 gauge, introduces the possibility of in-office vitrectomy for recurrent postoperative vitreous hemorrhage. Advantages of in-office vitrectomy include decreased travel for the patient, more flexibility in the schedule for the patient and surgeon, and a potential cost savings from reduced staffing and equipment needs. A case series illustrating the utility of in-office 3-port 27-gauge vitrectomy includes a case of vitreous hemorrhage after pars plana vitrectomy and specifically identifies this situation as one that may be particularly well served by in-office vitrectomy.¹³ In-office vitrectomy, however, carries the potential disadvantages of incomplete surgery and less sterility compared with an OR procedure.

ANTI-VEGF INJECTIONS

Anti-VEGF agents have become an option for treating vitreous hemorrhage after diabetic vitrectomy. A recent study showed that eyes with late vitreous hemorrhage after surgery had a significantly higher level of intravitreal VEGF compared to eyes that did not rebleed. In this study, a higher VEGF level was an independent predictor of rebleed.¹⁴ One study compared those who received bevacizumab every 2-3 weeks for postoperative vitreous hemorrhage to those who did not have pharmacologic treatment. They found that vitreous clearing time was 6.5 weeks for the bevacizumab treated eyes compared to 6.4 weeks for those who did not have pharmacologic treatment. However, none of the bevacizumab-treated patients required additional surgery compared to 27% of the nonpharmacologic treatment group.¹⁵

A similar study at our institution showed that repeated intravitreal bevacizumab can be used to treat recurrent vitreous hemorrhage after vitrectomy without requiring repeated surgery. Patients were treated at the time of hemorrhage and 7 of 8 had a clear vitreous at the next visit. Patients received a mean of 8 injections and had a mean of 4 recurrent hemorrhages. Those patients who had repeated hemorrhages were treated prophylactically at monthly intervals, which increased their time hemorrhage-free.¹⁶ A study comparing preoperative, intraoperative, and no bevacizumab intravitreal injection around the time of vitrectomy found that while preoperative bevacizumab was not helpful in decreasing the rate of postoperative vitreous hemorrhage, intraoperative injection was associated with a decrease in postoperative vitreous hemorrhage rate.¹⁷

MOST COMMON PRACTICES

The American Society of Retina Specialists (ASRS) Patterns and Trends (PAT) survey in 2014 addressed the issue of vitreous hemorrhage. To the question, “How do you manage persistent vitreous hemorrhage 1 week post-op after pars plana vitrectomy for proliferative diabetic retinopathy?” 68% responded they would observe for several weeks then go to surgery for no clearance; 22% would use bevacizumab then go to surgery if there was no response; and the remaining 3% would do an in-office air-fluid exchange.¹⁸

OUR CURRENT PRACTICE

In an informal poll of our colleagues, most preferred the following algorithm when dealing with vitreous hemorrhage after diabetic vitrectomy (Figure 1). At visits where the retina is not visible, a B-scan ultrasound is usually performed to ensure the retina is attached. For most patients, we would start with anti-VEGF treatment, either bevacizumab or ranibizumab. If there is no improvement in 4 weeks to 6 weeks after the injection, it may be repeated up to several more times until the hemorrhage has cleared. If there is no response, most would consider a vitrectomy, although one colleague was in favor of in-office air-fluid exchange. If at any point the eye became high risk due to uncontrolled IOP secondary to hemolytic or ghost cell glaucoma, presence of RD, a threat of corneal bloodstaining, or the patient’s inability to function due to lack of vision in his or her better seeing eye, then return to the operating room for vitrectomy would be warranted. RP

REFERENCES

1. Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010;376(9735):124-136.
2. Wubben TJ, Talwar N, Blachley TS, et al. Rates of vitrectomy among enrollees in a United States managed care network, 2001–2012. Ophthalmology. 2016;123(3):590-598.
3. Ostri C, Lux A, Lund-Andersen H, la Cour M. Long-term results, prognostic factors and cataract surgery after diabetic vitrectomy: a 10-year follow-up study. Acta Ophthalmol. 2014;92(6):571-576.
4. Khuthaila MK, Hsu J, Chiang A, et al. Postoperative vitreous hemorrhage after diabetic 23-gauge pars plana vitrectomy. Am J Ophthalmol. 2013;155(4):757-763.
5. Novak MA, Rice TA, Michels RG, Auer C. Vitreous hemorrhage after vitrectomy for diabetic retinopathy. Ophthalmology. 1984;91(12):1485-1489.
6. Sato T, Tsuboi K, Nakashima H, Emi K. Characteristics of cases with postoperative vitreous hemorrhage after 25-gauge vitrectomy for repair of proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2017;255(4):665-671.
7. Yeh PT, Yang CM, Yang CH, Huang JS. Cryotherapy of the anterior retina and sclerotomy sites in diabetic vitrectomy to prevent recurrent vitreous hemorrhage. Ophthalmology. 2005;112(12):2095-2102.
8. Neely KA, Scroggs MW, McCuen BW. Peripheral retinal cryotherapy for postvitrectomy diabetic vitreous hemorrhage in phakic eyes. Am J Ophthalmol. 1998;126(1):82-90.
9. Martin DF, McCuen BW 2nd. Efficacy of fluid-air exchange for postvitrectomy diabetic vitreous hemorrhage. Am J Ophthalmol. 1992;114(4):457-463.
10. Wu WC, Chen JY, Chen YC, Chang YC. Management of postvitrectomy diabetic vitreous hemorrhage with volume homeostatic fluid-fluid exchanger. Graefes Arch Clin Exp Ophthalmol. 2009;247(9):1183-1189.
11. Wu WC, Chang SM, Chen JY, Chang CW. Management of postvitrectomy diabetic vitreous hemorrhage with tissue plasminogen activator (t-PA) and volume homeostatic fluid-fluid exchanger. J Ocul Pharmacol Ther. 2001;17(4):363-371.
12. Yokota R, Inoue M, Itoh Y, Rii T, Hirota K, Hirakata A. Comparison of microinsicion vitrectomy and conventional 20-gauge vitrectomy for severe proliferative diabetic retinopathy. Jpn J Ophthalmol. 2015;59(5):288-294.
13. Shevchenko L, Westhouse SJ, Aaberg TM Jr.. When office-based vitrectomy makes sense. Ret Phys. 2014;11(3):23-27,52.
14. Wakabayashi Y, Usui Y, Tsubota K, et al. Persistent overproduction of intraocular vascular endothelial growth factor as a cause of late vitreous hemorrhage after vitrectomy for proliferative diabetic retinopathy. Retina. 2017. [Epub ahead of print]
15. Yeh PT, Yang CH, Yang CM. Intravitreal bevacizumab injection for recurrent vitreous haemorrhage after diabetic vitrectomy. Acta Ophthalmol. 2011;89(7):634-640.
16. Ferenchak K, Duval R, Cohen JA, MacCumber MW. Intravitreal bevacizumab for postoperative recurrent vitreous hemorrhage after vitrectomy for proliferative diabetic retinopathy. Retina. 2014;34(6):1177-1181.
17. Ahn J, Woo SJ, Chung H, Park KH. The effect of adjunctive intravitreal bevacizumab for preventing postvitrectomy hemorrhage in proliferative diabetic retinopathy. Ophthalmology. 2011;118(11):2218-2226.
18. Stone TW, ed. ASRS 2014 preferences and trends membership survey. Chicago: American Society of Retina Specialists.