Vitreoretinal surgeons have evaluated the use of pharmacologic intraoperative adjuncts since intravitreal steroid delivery for complex proliferative vitreoretinopathy (PVR) was pioneered by Dr. Robert Machemer and colleagues.1-3 Intravitreal surgical agents as diverse as 5-fluorouracil, heparin, and tissue plasminogen activator have been evaluated for intravitreal use in PVR.
Recent reports have focused on intraretinal edema, cyst, and persistent subretinal fluid as limiting factors in visual recovery in complex and common macular pathologies.4 Cataract surgeons have addressed issues related to postoperative cystoid macular edema and its management for over two decades. Recent data have suggested that inflammatory mediators play a major role in postoperative CME but may be modulated by underlying unique patient factors or intraoperative surgical events.5
Macular edema (ME) is a common cause of visual limitation in both post-vitrectomy eyes and those that have undergone phacoemulsification for cataract surgery. Although the incidence of ME after phacoemulsification has been well characterized, there are few data on CME after vitrectomy. Optical coherence tomography (OCT) has proven particularly advantageous in the diagnosis and analysis of ME over time, as it offers a quantitative as well as qualitative interpretation and is highly reproducible. Prior to OCT, studies by Staudt et al6 and McDonald et al7 showed evidence of leakage on postoperative angiography in 80% of macular hole surgeries and 70% of epiretinal membrane surgeries. Kim et7 al recently incorporated OCT into an investigation of post-vitrectomy ME, and reported that 47% of eyes undergoing vitrectomy for predominantly epiretinal membrane, macular hole, or vitreous hemorrhage had evidence of edema on postoperative OCT.
Combination of vitrectomy with phacoemulsification is increasingly utilized as means to facilitate intra- and postoperative viewing to the posterior segment. Additionally, combined procedures are performed to eliminate the risks and costs inherent to a second phacoemulsification surgery in a recently vitrectomized eye.9-12 Several small series have shown comparative improvement in postoperative visual acuity when vitrectomy was combined with phacoemulsification, with no associated rise in complication frequency.13-17
Both vitrectomy and phacoemulsification, as well as the combination of both surgeries, have been shown to induce ME that can negatively affect visual recovery. There has been considerable interest in surgical adjuvant medications to address this problem. The role of intravitreal agents, particularly antiinflammatory agents such as triamcinolone acetonide, have garnered recent interest.
This retrospective, consecutive case series from the Bascom Palmer Eye Institute presents pre- and postoperative OCT analysis in eyes that underwent combined phacoemulsification and vitrectomy with the use of intravitreal triamcinolone acetonide as an intraoperative pharmacologic adjunct targeted at decreasing postoperative ME. The primary objective was to analyze the incidence and resolution in ME after surgery.
PATIENTS AND METHODS
The study was performed with the approval of the
University of Miami Institutional Review Board and in accordance
with the US Health Insurance Portability and
Accountability Act and the Declaration of Helsinki guidelines.
A retrospective review was conducted of all patients who
underwent combined sutureless 23-gauge pars plana vitrectomy
with phacoemulsification cataract extraction between
January 1, 2006 and March 1, 2009 at the Bascom Palmer Eye
Institute by a single vitreoretinal and ocular oncology surgeon (TGM) and his vitreoretinal surgical fellows. All patients with
fewer than 6 months of follow-up were excluded. All patients
underwent surgery with the Accurus 2500 surgical system
(Alcon Laboratories, Inc., Fort Worth, TX) followed by utilization
of the Constellation Vision System (Alcon Laboratories,
Inc.). All patients had clinically significant lens opacification at
the time of combined surgery. Preoperative biometry for
intraocular lens (IOL) power was performed with the IOL
Master (Carl Zeiss Meditec, Dublin, CA). Postoperative clinic
evaluations were performed at 1 day, 1 week, 1 month, 3
months, 6 months, and 12 months. Refractions were performed
at 1 or 3 months postoperatively. Patients received
topical antiinflammatory, antibiotic, and cycloplegic drops
postoperatively when indicated.
SURGICAL PROCEDURE
After informed consent was obtained, patients received
local or general anesthesia. After a betadine preparation and
sterile draping, the 23-gauge trochars were inserted 3.5 mm
posterior to the limbus in a shallow beveled fashion then
directed perpendicularly toward the optic nerve. The superior
23-gauge ports were temporarily occluded and the infusion
cannula was connected but kept off until the phacoemulsification
portion of the procedure was completed.
Clear corneal incisions were created and viscoelastic was used to replace the aqueous. A 5- to 6-mm continuous curvilinear capsulorrhexis was initiated with a bent cystotome and completed with forceps. After hydrodissection and rotation, the nucleus was removed using a bimanual divide-and-conquer technique. The cortex was removed with automated aspiration, and the capsular bag was inflated with viscoelastic.
The 3-mm corneal wound was enlarged with a crescent blade to 4 mm. An acrylic foldable IOL (three-piece MA60AC or MA50BM, Acrysof [Alcon Laboratories, Inc.]) was preferentially placed in the capsular bag, but the ciliary sulcus was used when inadequate zonular or capsular support was present. Viscoelastic was left filling the anterior chamber. The corneal wound was closed with a single nylon suture.
Vitrectomy was performed using the AVI (Advanced Visual Instruments, Inc., New York, NY) 130° widefield viewing system. In some patients, vitrectomy was combined with other procedures, including membrane removal, encircling band placement, and use of internal tamponade. Intravitreal triamcinolone acetonide (IVTA; 4 mg/0.1 cc Triesence, Alcon Laboratories., Inc.) was injected into any eye not receiving tamponade following removal of the last cannula. Subconjunctival gentamicin (20 mg) and dexamethasone (4 mg) were administered at the conclusion of the procedure in all eyes.
Study characteristics recorded included age, gender, presence of diabetes, primary surgical indication, past ocular history, lens status, previous intraocular surgery, laser, and intravitreal injections. Pre- and postoperative visual acuity, intra- and postoperative complications, and postoperative interventions were recorded.
Preoperative and postoperative OCT was performed with the Stratus OCT3 machine (CZM, Dublin, CA) and then preferentially, with the Spectralis HRA+OCT (Heidelberg Engineering, Vista, CA) by a trained technician as member of a dedicated photography department. OCT images were generated with standard manufacturer protocol. Centerpoint thickness and central subfield thickness were measured in microns, and total macular volume in millimeters cubed. Values were obtained from the macular thickness map and data table, and the scans were evaluated retrospectively for artifact. Macular edema was defined as a central subfield thickness (CSF) equal to or greater than 272 µm, a value reported by Chan et al19 as three standard deviations above the mean thickness of 212 µm. This value was similarly employed by Kim et al8 in their study to define ME on OCT.
STATISTICAL ANALYSIS
Snellen visual acuities were converted to logMAR acuities
for data analysis. Acuities too poor or otherwise unable to
be assessed with Snellen charts were converted using the
following convention: count fingers (CF) = 20/2000; hand
motions (HM) = 20/20,000; and light perception (LP) =
20/200,000. LogMAR acuities were compared with baseline
values using the paired t-test and the nonparametric paired
Wilcoxon test with SSPS 17 software. OCT values were
compared using the paired t-test. Both eyes of two patients
were included as if they were independent observations in this analysis; however, a second analysis including only one
eye per patient gave the same results.
RESULTS
Baseline characteristics of the study cohort are listed in
Table 1. A total of 114 eyes from 111 patients underwent
combined 23-gauge sutureless vitrectomy with phacoemulsification
during the study period for various indications. Of
those eyes, 62 were excluded for not having a preoperative
OCT or a postoperative OCT within ninety days of surgery.
Of the remaining 52 eyes, 45 had received IVTA at time of
surgery, and were included in the primary analysis.
Mean age at surgery was 58.6 years, and mean follow-up was 334 days. Two eyes had previously undergone vitrectomy. All eyes were phakic prior to surgery. Three eyes were of diabetic patients. Primary indication for surgery was refractory cystoid macular edema in 10, radiation retinopathy in 13, epiretinal membrane in four, vitreous hemorrhage in one, coloboma in one, dislocated lens in one, macular schisis in two, retinal detachment in four, retinal and choroidal vascular tumors in six, Coats disease in two, and uveal effusion syndrome in one. Twelve eyes had optic nerve compromise from prior radiation optic neuropathy. Surgery included membrane peeling in 30, endolaser in 15, fluid-air exchange and gas tamponade in two, iris retractors in three, and silicone oil removal in two. Thirty-one required additional intravitreal injections after surgery (13 for CME, four for wet AMD, eight for radiation retinopathy, two for diabetic macular edema, two for neovascular glaucoma, and two for CNVM secondary to angioma). YAG capsulotomy for posterior capsular opacification was performed in 10 eyes.
Mean visual acuity was the same at 1 week postoperatively (20/150-1, logMAR 0.92) compared with baseline (20/150-2, logMAR 0.93), but improved through each subsequent measurement. Improvement was seen at 3 months (20/100-3, logMAR 0.85) and at 6 months (20/100-1, logMAR 0.78). At 3 months 19 (42%) gained two or more lines of vision, and seven (16%) lost two or more lines.
OCT thickness decreased overall an average of 9 µm per CMT, 8 µm per CSF, and 0.1 mm3 per macular volume without reaching statistical significance. In the 18 patients with preoperative OCT evidence of ME, thickness decreased by 46 µm per CMT (P=.26), 47 µm per CSF (P=.22), and 0.5 mm3 per macular volume (P=.30). In the 27 patients without preoperative ME, the respective decreases were 8 µm per CMT (P=.62), 7 µm per CSF (P=.56), and 0.2 mm3 per macular volume (P=.69). None of these changes proved statistically significant.
Seven patients in the series met inclusion criteria regarding preoperative and postoperative OCT and underwent vitrectomy with phacoemulsification but without intraoperative IVTA. They were analyzed as a small comparison population to the larger group that received IVTA. Of these seven, four had preoperative ME and experienced postoperative OCT thickness increases of 95 µm per CSF, 81 µm per CSF, and 2.2 mm3 per macular volume. Three lacked preoperative ME and had similar increases of 150 µm, 160 µm, and 2.6 mm3. Thus this small group experienced worsening edema after surgery.
Retinal detachment occurred in four patients after surgery, two of which were recurrent detachments, and one of which was an exudative detachment in a patient with a choroidal hemangioma. There were no cases of suprachoroidal hemorrhage or endophthalmitis. Other intraand postoperative complications included capsular tear in eight, zonular dehiscence in one, blepharoptosis in one, and hypotony in one eye requiring repeated postoperative intravitreal triamcinolone injections.
Mean intraocular pressure (IOP) rose from a preoperative baseline of 16.0 to 19.0 on postoperative day 1, but normalized to 16.6 by postoperative month 1, and had decreased to 14.8 by month 3 and 13.8 by month 6. Eleva-ted IOP (>25 mm Hg) was noted postoperatively in four eyes, two of which appeared steroid-related, and one of which required the Baerveldt implant (Abbott Medical Optics, Inc., Irvine, CA). The other two eyes with elevated IOP postoperatively had neovascular glaucoma from radiation retinopathy, and both eventually required enucleation.
DISCUSSION: Intravitreal Corticosteroids: A Review of Therapeutic and Surgical Applications
Post-vitrectomy ME remains imperfectly characterized by
existing literature, but recent studies have begun to utilize
OCT to further our understanding of this common problem.
Even less is known about the incidence of ME that follows
combined surgery involving vitrectomy and phacoemulsification,
a technique that is gaining increasing interest and
applicability to a variety of clinical situations. This retrospective series was organized to characterize the OCT findings
associated with combined vitrectomy and phacoemulsification
with an intravitreal antiinflammatory agent in the form
of TA.
The recent study by Kim et al8 demonstrated a 47% incidence of ME on OCT after vitrectomy alone. The combination of vitrectomy and phacoemulsification would reasonably seem to have no less of a tendency towards ME than either procedure alone, and perhaps if anything, combined surgery would be more likely to cause postoperative edema. In this series of combined surgery the postoperative ME incidence was 40%, which was actually the same as the preoperative ME on OCT (40%). The mean retinal thickness by each of three recorded parameters likewise decreased in this study group, most dramatically when there was already preoperative edema. This relative improvement in retinal thickness could be attributed to the adjuvant IVTA injection that these patients received at the time of surgery. The worsening thickness values on OCT for the seven patients who did not receive IVTA seems to support this possibility, but that group was particularly small, and this retrospective study carries risk of selection bias.
Another issue that this study presents is the appropriateness of quantitative OCT measurements for the diagnosis and interpretation of ME. Other causes of intra- or subretinal fluid or thickening can complicate the retina thickness values. Several patients in this study had coexisting epiretinal membranes and macular edema, and determination of the primary disease process in these patients relied on qualitative OCT interpretation. When the membrane appeared to be the direct cause of retinal thickening, and the membrane peel seemed the reason for decreased thickness postoperatively, that eye was excluded from OCT thickness analysis. However, other cases with coexistent ME and epiretinal membranes were more ambiguous, and the categorization and analysis of these eyes is problematic.18
This study has several important limitations. It is retrospective in nature, and while 114 consecutive cases were analyzed, data was limited in a large subset due to inadequacies in postoperative OCT imaging. The time interval between surgery and the pre- and postoperative OCTs varied, and the mean postoperative interval was 6 weeks, 2 weeks longer than that of the study by Kim et al.8 The additional 2 weeks affords more time for macular edema to spontaneously resolve, which may have accounted for the lower incidence than in the Kim study. This patient series was that of a vitreoretinal specialist whose practice has a large component of ocular oncology. The diagnoses and indications for surgery in his patients were quite different from those of a more typical retina practice. This study also introduced two variables— combined surgery and intravitreal triamcinolone—that individually have not been previously studied with the use of OCT to look for ME, complicating interpretation of the data.
Nonetheless, this study, along with those discussed in this article, sets the stage to consider intraoperative pharmacotherapy as a major advance in the surgical armamentarium of the vitreoretinal surgeron. The lack of demonstrable toxicity, the ease of delivery, and the ability to influence postoperative factors that affect anatomic results and patient visual functional outcomes greatly extends the reach of the surgeon in the management of both basic and complex macular pathologies. We owe a debt of gratitude to Dr. Robert Machemer and colleagues for initiating the study of intraoperative surgical pharmacotherapy.
Timothy G. Murray, MD, MBA, FACS, is Professor of Ophthalmology and Radiation Oncology at the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine. Dr. Murray is a consultant for Alcon Laboratories, Inc. He can be reached at +1 305 326 6000, ext. 6166; fax: +1 305 326 6147; or via e-mail at tmurray@med.miami.edu.
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