Comorbid Conditions in Vitreoretinal Surgery

Awareness of existing health conditions improves surgical results.

SHAWN WILKER, MD · JULIA A. HALLER, MD · DIANA V. DO, MD

Comorbidities such as systemic hypertension, diabetes mellitus, and cardiovascular disease are common in patients who need ophthalmic surgery.^1-3 Many of these comorbidities have the potential to influence the timing of surgery, as well as to have an impact on decisions that are made in the preoperative, intraoperative, and postoperative periods. Understanding the risks associated with comorbidities and how they may be minimized is essential for the vitreoretinal surgeon, both in making informed decisions in the preoperative, intraoperative, and postoperative periods and in responsibly advising potential surgical patients. This report will review the literature with regard to how comorbidities can influence surgical decisions and surgical outcomes in vitreoretinal surgery.

PREOPERATIVE EVALUATION AND TESTING

The Joint Commission for the Accreditation of Hospitals requires all surgical patients to have a history and physical examination documented in the medical record within 30 days of surgery. The components of this history or physical, however, are not defined. Often, patients will be referred to their primary physician for preoperative evaluation, but, in times of urgency, the ophthalmologist is often the person who performs this task. Significant pre-existing medical disease in patients undergoing ophthalmic surgery has been reported in 62.5% to 81% of adult patients.^1-3 A thorough history and physical exam can often elicit the presence of underlying systemic disease that can then guide preoperative testing or further management.

Routine preoperative medical testing prior to elective surgery has been questioned.^4-10 Approximately $30 billion is spent in health care annually for preoperative testing for all types of surgery.⁴ In a national survey comparing the preoperative routines of ophthalmologists to anesthesiologists and internists, 50% of ophthalmologists reported frequently obtaining a chest x-ray in a patient without a history of major medical illness but who was scheduled for cataract surgery.¹¹ This rate was significantly higher when compared to 40% of internists and 33% of anesthesiologists who would order a chest x-ray in the same patient. Many respondents (32% to 80%) believed tests were unnecessary but cited multiple reasons for obtaining tests (eg, medical-legal concerns and institutional requirements). When routine preoperative medical testing in cataract surgery was evaluated in 19 557 elective cataract operations by Schein and associates,¹² there were no significant differences in the intraoperative and postoperative event rates between patients who did or did not receive a standard battery of medical tests (electrocardiography, complete blood count, and measurement of serum levels of electrolytes, urea nitrogen, creatinine, and glucose).

MORBIDITY AND MORTALITY IN OPHTHALMIC SURGERY

While ophthalmic surgery is not classified as high-risk surgery, a few studies have looked at perioperative morbidity and mortality associated with ophthalmic surgery.^13-15 Quigley¹³ looked at the mortality rate over a 20-year period by reviewing all of the records from the Wilmer Eye Institute at Johns Hopkins University for the years 1952 though 1972. The "adjusted" mortality rate of 0.1% was reported for deaths that might have been due to ophthalmic admission and surgery.¹³ In this study, charts were reviewed for any patient who was on the Wilmer Eye Institute inpatient ophthalmic service at any time. While fewer patients are admitted today for ophthalmic surgery, an interesting observation was made about the mortality rate in patients who had undergone retinal surgery. The rate of mortality for retinal detachment patients was more than twice the contributory patient rate, and this difference was statistically significant. Patients undergoing vitreoretinal surgery were more likely to have received general anesthesia and to be slightly younger, and they were 3 times more likely to be on postoperative bed rest. In this report, pulmonary embolism (PE) was the most common cause of death, followed by unknown reasons (no autopsy) and myocardial infarction (MI). Despite the fact that more patients now have retinal surgery in an ambulatory setting, concern has been raised about the possible increased risk of thromboembolic events in patients who undergo general anesthesia and in those for whom postoperative positioning is required. In a review of patient charts of vitreoretinal or ocular oncologic surgical cases performed under general anesthesia, the incidence of serious complications (MI, PE, and deep venous thrombosis) was 1.8% among vitreoretinal procedures. The authors recommended prophylactic measures to minimize the risk of thromboembolic disease in patients at moderate to high risk, including intermittent pneumatic leg compression or short-term anticoagulation.¹⁵

SYSTEMIC HYPERTENSION

Sprague¹⁶ first identified an association between hypertension and a perioperative cardiac risk in 1929. Aside from the anesthesia risk, the retinal surgeon should also be aware of potential intraoperative complications that can arise from uncontrolled hypertension. Suprachoroidal hemorrhage is a rare but potentially devastating complication that has been reported to have an incidence between 0.17% and 1.9% for retina and vitreous surgery.^17-19 While reviewing the risk factors of suprachoroidal hemorrhage during pars plana vitrectomy (PPV), Tabandeh and associates²⁰ found that intraoperative systemic hypertension was a significant risk factor. Elevated systolic blood pressure at the time of PPV has also been reported in 3 other smaller studies to be a significant risk factor for suprachoroidal hemorrhage.^21-23

Treating systemic hypertension prior to surgery is also important and may have a role in decreasing the risk for postoperative hemorrhage in patients undergoing PPV for nonclearing vitreous hemorrhage secondary to proliferative diabetic retinopathy (PDR) (Figure). Soto-Pedre and associates24 performed a case-control retrospective study looking at the risk factors for postoperative hemorrhage after vitrectomy for diabetic retinopathy (DR). Nineteen cases and 49 controls were matched on surgeon and the date of surgery. Patients who had used antihypertensive agents within 3 months before vitrectomy showed only one-fifth the risk for postoperative vitreous hemorrhage compared to patients who were not using antihypertensive medications.

Figure. A fundus photo of an example of proliferative diabetic retinopathy.

DIABETES MELLITUS

Results from the Wisconsin Epidemiologic Study showed that frequency and severity of macular edema were closely associated with glycemic control in both type 1 diabetics using insulin and older-onset type 2 diabetics using different glycemic agents.^25-26 There is evidence that preoperative glycemic control may also influence the likelihood of macular edema reduction in eyes undergoing vitrectomy for persistent diabetic macular edema (DME). Kojima and associates²⁷ used multiple logistic regression analysis to show that the HgbA1C level was inversely associated with the improvement of foveal thickness after other factors were controlled. Patients in their study had a 0.54 lower probability of foveal thickness improvement for every 1% HgbA1C rise on laboratory results obtained up to 2 weeks prior to vitrectomy.

In the Early Treatment of Diabetic Retinopathy Study Report, cataract surgery did not affect the incidence of macular edema, but the possibility of an increase in the severity of edema was suggested.²⁸ In contrast, other investigators have suggested that lens extraction during PPV for DR may be associated with a decrease in the severity of DME. In the patients who Kojima and associates²⁷ evaluated for improvement in foveal thickness after vitrectomy for DME, 53% had cataract surgery with intraocular lens (IOL) implantation at the time of vitrectomy.²⁷ In this study, postoperative pseudophakia had an independent odds ratio for foveal-thickness improvement of 9.6 relative to postoperative phakia. However, additional studies are needed to further investigate this observation and to determine whether cataract extraction affects macular edema in patients with DR.

Due to an increased incidence of postoperative anterior-segment neovascularization and observations that the crystalline lens added a protective barrier from the risk of progression of DR, many retinal surgeons previously responded by attempting to spare the crystalline lens (lens-sparing vitrectomy).^29-33 As vitreoretinal and anterior-segment surgical techniques and instrumentation have improved over the past decade, many retinal surgeons have reported on combining PPV with lens extraction and IOL implantation.^34-40 Schiff and associates⁴¹ compared eyes that remained phakic after vitrectomy vs eyes that were either aphakic or pseudophakic postoperatively. One hundred two eyes that had undergone vitrectomy for PDR were reviewed. Eyes that were phakic after primary diabetic vitrectomy had a significantly higher rate of subsequent vitreoretinal reoperation when compared with aphakic and pseudophakic eyes. This was secondary to higher rates of postoperative rhegmatogenous retinal detachment and nonclearing vitreous hemorrhage requiring reoperation. However, the authors noted that the lens status of the eye did not affect the ultimate anatomic and visual outcomes of primary diabetic vitrectomy. Therefore, the decision for lens extraction can be made by the retinal surgeon as deemed necessary for each individual case. Proper patient selection is necessary, however, as combined surgery is not recommended for patients with severely ischemic eyes, iris neovascularization, or severe tractional retinal detachment.^42,43

Approximately one-third of patients who undergo PPV for PDR will develop postoperative recurrent vitreous hemorrhage.^24,44,45 In many cases, fibrovascular ingrowth at the sclerotomy sites has been reported to be the etiology of the recurrent postoperative vitreous hemorrhage.^46,47 A study by Hershberger and associates⁴⁸ using ultrasound biomicrosopy identified varying levels of fibrovascular ingrowth at the sclerotomy sites of 85% of eyes with recurrent, nonclearing postoperative vitreous hemorrhage after vitrectomy for PDR. Factors associated with development of prominent, clinically important fibrovascular ingrowth at sclerotomy sites after PPV include PDR, incomplete posterior vitrectomy, larger sclerotomy incisions, pronounced postoperative inflammation at the sclerotomy sites, and poor surgical closure of the sclerotomy wound.⁴⁹ Authors have reported success in using endolaser in a near-confluent pattern from the equator to the ora serrata and in using cryotherapy of the anterior retina and sclerotomy sites in hopes of decreasing the risk of fibrovascular ingrowth.^45,50 Prospective studies are needed to determine whether these interventions decrease the likelihood of postoperative hemorrhage.

END-STAGE RENAL DISEASE AND HEMODIALYSIS

In 1991, Gollamudi and associates⁵¹ reported the 5-year postoperative survival rate in patients undergoing vitreoretinal surgery for complications secondary to DR. In this study, the 5-year survival rate was 74.7% and renal disease was a comorbidity associated with a lower survival.

Historically, surgery was deferred in patients with endstage renal disease on hemodialysis because of the concern of increased mortality among these individuals. Recently there has been an improvement in the management of diabetic end-stage renal disease resulting in longer survival rates and subsequently, these patients have become more likely to be candidates for vitreoretinal surgery.⁵² Nawrocki⁵³ reported on 9 eyes of 7 patients with type 1 diabetes who were on hemodialysis in which vitrectomy with silicone oil tamponade was performed. All eyes had nonclearing vitreous hemorrhage with advanced PDR and 5 eyes had additional tractional retinal detachments. Visual outcomes were similar to those in published data for patients without end-stage renal disease who had vitreoretinal surgery for PDR.

Despite reports that a poor visual outcome after vitrectomy for PDR had been observed in patients with hypoalbuminemia and anemia secondary to diabetic nephropathy,^54,55 Hayashi⁵⁶ reported that renal failure and hemodialysis did not appear to have a deteriorative influence on the outcome of vitrectomy for PDR. Dialysis was scheduled for the day before and the day after surgery in the study. Again, no remarkable difference was found among surgical outcomes in this series compared with published data on diabetic vitrectomy in which most patients did not have renal failure. A flat anterior chamber was seen in 2 out of 76 eyes, which the authors had noted had not been seen in more than 1000 non-nephropathic diabetic patients after vitrectomy in their practice. Because of patients' difficulty with maintaining a prone position during hemodialysis, face-down positioning was obtained by having patients lie on their side and flex their arm with an artificial arteriovenous shunt while rotating their neck to a face-down position. The authors theorized that, because patients had difficulty with positioning, many were frequently lifting their faces up during hemodialysis. Floating gas bubbles then pushed the iris toward the cornea leading to an irreversible flat anterior chamber. They made a recommendation that special attention should be given to adequate positioning of the patient's face during hemodialysis to avoid these and other complications.

ANTICOAGULATION

Many comorbidities such as atrial fibrillation, cerebrovascular attack, and pulmonary embolisms are treated by placing a patient on life-long anticoagulation with agents such as aspirin, clopidogrel (Plavix, Sanofi-Aventis/Bristol-Myers Squibb), or warfarin. Frequently, a vitreoretinal surgeon is faced with the decision to continue or discontinue these medications in order to lower the potential risk of bleeding during surgery. The risk of catastrophic bleeding can occur both during local anesthesia, such as a peribulbar or retrobulbar blocks, as well as during the actual vitreoretinal procedure. These risks, however, need to be weighed against the concern about the increased risk of thromboembolism and stroke while the patient is off of their anticoagulant medication. Furthermore, there may be rebound hypercoagulability that can occur after the abrupt cessation of anticoagulation.^57-59

A study at the Helsinki University Eye Hospital⁶⁰ evaluated hemorrhage and risk factors associated with inferolateral retrobulbar and peribulbar blocks. One thousand three hundred eighty-three patients were prospectively followed prior to ocular surgery. Patients were advised to discontinue warfarin for 2 days and aspirin for 3 days prior to surgery. They were interviewed just prior to the surgery as to whether they had discontinued taking these medications and, if so, how long before surgery. The overall frequency of hemorrhages, including varying degrees of lid hemorrhages and retrobulbar hemorrhages, was 4%. No retrobulbar hemorrhages that resulted in elevated IOP occurred during this series, while periocular lid ecchymosis without an increase in IOP did occur in 7 patients (0.5%). Warfarin was used by 5.5% of the patients. Of those patients that were on warfarin, 28.8% discontinued it 0 to 2 days prior to surgery. No predisposition to hemorrhage was seen. Preoperative use of aspirin did not increase the frequency or grade of hemorrhage. Furthermore, the interval of discontinuation of aspirin did not affect the rate of hemorrhage. The authors concluded that in their study population there seemed to be no reason to limit the use of aspirin for blocks. The authors did state that their study supported the assumption that discontinuation of warfarin for 2 days preoperatively might be sufficient to maintain hemostasis to prevent bleeding during retrobulbar/peribulbar blocks.

The literature on the safety of continuing anticoagulation during vitreoretinal surgery is limited. Flaxel and Blach⁶¹ reported 3 patients on aspirin who had intraoperative hemorrhages during vitreoretinal surgery. In contrast, Narendran and Williamson⁶² reported that aspirin did not appear to increase the risk of hemorrhage. In the 7 patients taking warfarin included in their study, the use of warfarin was significantly associated with the occurrence of choroidal hemorrhage and postoperative diabetic vitreous hemorrhage. Fu and associates⁶³ reported on 25 patients who underwent vitreoretinal procedures while on warfarin. One patient who underwent scleral buckling and external drainage of subretinal fluid had an intraoperative subretinal hemorrhage that was associated with the drainage procedure. However, it is unclear if the subretinal hemorrhage was due to warfarin use since hemorrhage is a reported adverse event following drainage of subretinal fluid.⁶⁴ In all other patients, no intraoperative complications occurred. The authors noted that was extensive dissection of fibrovascular proliferation was not performed in any of the patients.

Investigators at the Washington University School of Medicine performed a review evaluating the risk of hemorrhagic complications associated with vitreoretinal surgery in patients in whom warfarin was continued throughout the surgical period. Fifty-four patients who underwent 57 PPVs were reviewed.⁶⁵ The international normalized ratio (INR) was obtained on the day of surgery, and patients were divided into groups based therapeutic level of INR. Patients were concomitantly kept on aspirin and clopidogrel if previously using these medications. No patients in the study, regardless of INR level, experienced intraoperative hemorrhages. In patients with INRs between 1.2 and 1.49 (highly therapeutic), there were 2 (5%) procedures associated with postoperative hemorrhages. In the group with INRs above 2.5 (supratherapeutic), there were 2 (17%) procedure that had postoperative hemorrhages. Among the 4 patients with postoperative hemorrhages, 1 patient with an INR of 1.41 also was on aspirin and another patient with an INR of 2.69 had an elevated partial thromboplastin time of 55.3 seconds.

SUMMARY

Comorbidities are frequent in patients undergoing vitreoretinal surgeries. Coexisting medical illnesses and medication use have the potential to influence both ocular outcomes and systemic adverse events following vitreoretinal surgery. The current medical literature suggests collaborating with internists to optimize control of diabetes mellitus, hypertension, and other chronic comorbidities before embarking on vitreoretinal surgery. Understanding the risks associated with comorbidities and how they may be minimized is essential for the vitreoretinal surgeon, both in guiding decision-making in the preoperative, intraoperative, and postoperative periods and in responsibly advising potential surgical patients. RP

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