Ophthalmic Surgery, Lasers and Imaging Retina

Clinical Science 

Erosive Retinopathy and Retinal Detachment From Depot Intravitreal Triamcinolone Acetonide Injection at the End of Pars Plana Vitrectomy

Robert A. Sisk, MD, FACS; Yogin P. Patel, MD; Robert E. Foster, MD; Michael R. Petersen, MD, PhD

Abstract

BACKGROUND AND OBJECTIVE:

Intravitreal triamcinolone acetonide (IVTA) used as a surgical adjuvant for pars plana vitrectomy (PPV) can stain cortical vitreous, control postoperative inflammation, and reduce retinal edema. Sterile endophthalmitis uncommonly complicates office-based IVTA injection. The authors report a new complication of IVTA depot injection at the end of PPV.

PATIENTS AND METHODS:

Retrospective records review of all patients treated at the Cincinnati Eye Institute with PPV between January 1, 2011, and December 31, 2017, who developed a triad of sterile endophthalmitis, atrophic retinal breaks under the depot IVTA in the inferior retina, and rhegmatogenous retinal detachment (RRD). Eyes with flap tears, solely superior breaks, or stretch holes from proliferative vitreoretinopathy causing RRD were excluded.

RESULTS:

Eight eyes of eight patients (four males and four females; mean age: 73.7 years) who received 4 mg or 8 mg IVTA depot at the end of PPV surgery presented at a mean of 23.5 days following PPV with RRD (one macula-involving, seven macula-sparing), requiring treatment with PPV in six eyes and laser retinopexy alone in two eyes. Seven eyes that underwent membrane peeling (MP) received IVT to prevent cystoid macular edema (CME) and one eye with prior MP was treated for CME. Mean vitreous inflammation was 2+ cell at 1 week postoperatively. Two patients had documented sterile endophthalmitis within the first week requiring vitreous cultures and antibiotics injections. Visual acuity (VA) for eyes requiring PPV for RD repair declined from 20/90 preoperatively to 20/212 at 6 months postoperatively. VA for eyes amenable to laser alone improved from 20/53 to 20/35. All eyes remained attached, with the exception of one patient who refused further treatment after developing recurrent detachment from PVR.

CONCLUSIONS:

Particle-induced sterile endophthalmitis from IVTA depot at the end of PPV surgery resulted in atrophic inferior retinal breaks and RRD as a newly described entity coined “erosive retinopathy.” All retinal detachment surgeries required silicone oil tamponade. Poor visual outcome at 6 months was common for eyes requiring PPV for RD repair. The authors recommend avoiding IVTA depot injection at the end of PPV.

[Ophthalmic Surg Lasers Imaging Retina. 2019;50:613–619.]

Abstract

BACKGROUND AND OBJECTIVE:

Intravitreal triamcinolone acetonide (IVTA) used as a surgical adjuvant for pars plana vitrectomy (PPV) can stain cortical vitreous, control postoperative inflammation, and reduce retinal edema. Sterile endophthalmitis uncommonly complicates office-based IVTA injection. The authors report a new complication of IVTA depot injection at the end of PPV.

PATIENTS AND METHODS:

Retrospective records review of all patients treated at the Cincinnati Eye Institute with PPV between January 1, 2011, and December 31, 2017, who developed a triad of sterile endophthalmitis, atrophic retinal breaks under the depot IVTA in the inferior retina, and rhegmatogenous retinal detachment (RRD). Eyes with flap tears, solely superior breaks, or stretch holes from proliferative vitreoretinopathy causing RRD were excluded.

RESULTS:

Eight eyes of eight patients (four males and four females; mean age: 73.7 years) who received 4 mg or 8 mg IVTA depot at the end of PPV surgery presented at a mean of 23.5 days following PPV with RRD (one macula-involving, seven macula-sparing), requiring treatment with PPV in six eyes and laser retinopexy alone in two eyes. Seven eyes that underwent membrane peeling (MP) received IVT to prevent cystoid macular edema (CME) and one eye with prior MP was treated for CME. Mean vitreous inflammation was 2+ cell at 1 week postoperatively. Two patients had documented sterile endophthalmitis within the first week requiring vitreous cultures and antibiotics injections. Visual acuity (VA) for eyes requiring PPV for RD repair declined from 20/90 preoperatively to 20/212 at 6 months postoperatively. VA for eyes amenable to laser alone improved from 20/53 to 20/35. All eyes remained attached, with the exception of one patient who refused further treatment after developing recurrent detachment from PVR.

CONCLUSIONS:

Particle-induced sterile endophthalmitis from IVTA depot at the end of PPV surgery resulted in atrophic inferior retinal breaks and RRD as a newly described entity coined “erosive retinopathy.” All retinal detachment surgeries required silicone oil tamponade. Poor visual outcome at 6 months was common for eyes requiring PPV for RD repair. The authors recommend avoiding IVTA depot injection at the end of PPV.

[Ophthalmic Surg Lasers Imaging Retina. 2019;50:613–619.]

Introduction

Rhegmatogenous retinal detachment (RRD) complicates 1% to 10% of cases of pars plana vitrectomy (PPV), most commonly acutely from insufficiently treated iatrogenic or preexisting retinal breaks, or in a delayed fashion from traction associated with proliferative vitreoretinopathy (PVR).1–5 Iatrogenic retinal breaks during PPV can be induced by excessive traction from the vitreous cutter, direct contact with intraocular instruments, or from a jet of injected fluid.1–5 Retinal breaks associated with posterior uveitis occur in a delayed fashion from retinitis and retinal necrosis associated with infectious or noninfectious antigens.6–8

Intravitreal triamcinolone acetonide (IVTA) has been used therapeutically for posterior uveitis, exudative retinal diseases, and retinal vein occlusions.9–18 Intraoperatively during PPV, IVTA can be used as a surgical adjuvant to enhance vitreous visualization.19–22 IVTA depot at the end of vitrectomy has been utilized to reduce macular edema following membrane peeling (MP) for idiopathic epiretinal membranes (ERMs),23–25 to reduce inflammation and proliferative vitreoretinopathy in retinal detachment surgery requiring silicone oil tamponade,26–29 and to reduce inflammation after vitrectomy for open globe trauma.30

Common complications of IVTA include ocular hypertension and accelerated cataract formation.31 Sterile endophthalmitis has been reported with 1% to 4% of office-based injections of IVTA.32–36 Various mechanisms have been proposed for this phenomenon, including reaction to preservatives and particle-induced inflammation. Particle size among various versions of IVTA have been compared, and the incidence of particle-induced inflammation was observed to be greatest with Triesence (Alcon, Fort Worth, TX), a U.S. Food and Drug Administration (FDA)-approved preservative-free version of IVTA that had the smallest particle size among versions of IVTA compared.32

(A) Ultra-widefield (UWF) fundus photography of inferior macula-sparing rhegmatogenous retinal detachment (RRD) in the right eye of Patient 8 associated with large atrophic breaks well demarcated 39 days after laser retinopexy. The patient did not require further treatment and maintained 20/60 vision. (B) UWF color image of the right eye of Patient 6 after repair of RRD with silicone oil tamponade. A visually significant cataract impaired visualization, but one can appreciate inferior laser retinopexy around atrophic breaks. (C) UWF color and (D) fundus autofluorescence (FAF) images of the left eye of Patient 7 demonstrates similar configuration of atrophic retinal breaks with corresponding window defects on FAF imaging within diffuse hypoautofluorescent RRD. Laser demarcation helped maintain a 20/20 outcome.

Figure 1.

(A) Ultra-widefield (UWF) fundus photography of inferior macula-sparing rhegmatogenous retinal detachment (RRD) in the right eye of Patient 8 associated with large atrophic breaks well demarcated 39 days after laser retinopexy. The patient did not require further treatment and maintained 20/60 vision. (B) UWF color image of the right eye of Patient 6 after repair of RRD with silicone oil tamponade. A visually significant cataract impaired visualization, but one can appreciate inferior laser retinopexy around atrophic breaks. (C) UWF color and (D) fundus autofluorescence (FAF) images of the left eye of Patient 7 demonstrates similar configuration of atrophic retinal breaks with corresponding window defects on FAF imaging within diffuse hypoautofluorescent RRD. Laser demarcation helped maintain a 20/20 outcome.

Herein we report a novel complication associated with Triesence depot injection at the end of PPV presenting as a triad of pseudoendophthalmitis, inferior retinal breaks underlying the drug depot, and associated RRD unassociated with vitreous traction. Although IVTA depot has been performed in eyes following PPV, to the best of our knowledge, there is no previous report of this complication.

Patients and Methods

We performed an institutional review board-approved, retrospective records review of all patients treated at the Cincinnati Eye Institute between January 1, 2011, and December 31, 2017, with PPV who received intravitreal Triesence (IVT) depot injection at the end of the procedure. Patients who developed RRD associated with atrophic retinal breaks underlying the IVT depot with or without noted sterile endophthalmitis were included. Eyes with flap tears (implying vitreous traction), solely superior breaks, or stretch holes from proliferative vitreoretinopathy causing RRD were excluded.

Surgical Technique

Three-port small-gauge PPV was done in standard fashion with using a Constellation (Alcon, Fort Worth, TX). Two eyes had concomitant phacoemulsification and posterior chamber intraocular lens implantation. Membrane peeling was performed with forceps and/or membrane scrapers assisted by heavy indocyanine green staining of the internal limiting membrane as previously described.37,38 Triesence was administered both as a vitreous stain (12 mg in 0.3 cc diluted to 1 cc with balanced salt solution, of which approximately 0.1 cc was used) and as a depot injection (4 mg/0.1 cc or 8 mg/0.2 cc) at the end of vitrectomy. Triesence was selected among other choices of IVTA because of its FDA-approved indication for vitreous staining, but the decision to leave depot injection at the end of PPV was at the discretion of the surgeon to reduce postoperative retinal edema. All but one eye received a 40% partial fluid-air exchange to facilitate sclerotomy closure. The infusion was removed after the intravitreal injection of Triesence, and subconjunctival cefazolin and dexamethasone injections were given.

Postoperative visits were performed at 1 day, 1 week, and 1 month after surgery, and as indicated by examination findings. Inflammation was graded based on the updated SUN Classification39 and treated with the same topical steroid drops prescribed for the surgery. Two patients with findings concerning for infectious endophthalmitis underwent vitreous aspiration for culture by 25-gauge needle and intravitreal injection of antibiotics (vancomycin 1.0 mg and ceftazidime 2.25 mg) and preservative-free dexamethasone (0.4 mg), but cultures and stains were negative.

All eyes presented with RRD within the first operative month from inferior atrophic retinal breaks. All patients underwent retinal detachment repair in a timely fashion using standard techniques.

Statistical Analysis

Main outcome measures were retinal attachment status and best-corrected visual acuity (VA). Secondary outcome measures were anterior chamber and vitreous inflammation and intraocular pressure. Statistical analysis was performed using Excel 2017 (Microsoft, Redmond, WA). VAs were converted from Snellen to logMAR for analysis. The null hypothesis was rejected when the P value was less than .05.

Results

Patient demographics are presented in Table 1. Eight eyes of eight patients (four males and four females; mean age: 73.7 years) who received 4 mg or 8 mg IVT depot at the end of PPV surgery presented at a mean of 23.5 days postoperatively with RRD (one macula-involving, seven macula-sparing). Seven eyes received IVT to prevent retinal edema from peeling of ERMs, and one eye with prior MP received IVT to treat cystoid macular edema. All eight eyes underwent uncomplicated repair of their retinal detachments. PPV was employed in six eyes, and laser retinopexy alone was used for two eyes. There were often multiple near-contiguous or large inferior breaks that appeared atrophic versus necrotic. There was no vitreous traction or secondary membrane formation from proliferative vitreoretinopathy observed to scleral depressed examination or seen intraoperatively during the PPV. These were the only retinal breaks seen pre-operatively and intraoperatively and were determined to be causative of the RRD.

Patient Demographics

Table 1:

Patient Demographics

Surgical outcomes are presented in Table 2. Only one eye had significant postoperative inflammation 1 day after PPV. Mean anterior chamber and vitreous inflammation increased to 0.5+ cell and 2+ cell, respectively, at 1 week postoperatively. On biomicroscopy, it was challenging to distinguish IVT crystals suspended in the vitreous from inflammatory cells. Fibrin and retinal hemorrhages were not observed. Two eyes had vitreous haze and 2+ vitreous cell or greater within the first week concerning for infectious endophthalmitis, and vitreous aspirate for cultures and intravitreal antibiotics injections were performed. Gram stains and cultures were negative. No eye received any additional undiluted triamcinolone after the secondary retinal detachment case. These patients had no previous mention of allergy, hypersensitivity, or adverse effect with steroid medication, and they all used postoperative steroid eye drops without further complication.

Surgical Outcomes Surgical Outcomes

Table 2:

Surgical Outcomes

Mean Snellen VA for eyes requiring secondary PPV for RRD repair declined from 20/108 preoperatively to 20/213 at six months postoperatively (P = .28). Mean Snellen VA for eyes amenable to laser alone improved from 20/53 to 20/35 (P = .18). All eyes remained attached with the exception of one, a patient who declined further treatment after developing late recurrent retinal detachment from proliferative vitreoretinopathy (PVR). No eyes experienced persistent ocular hypertension or profound hypotony.

Discussion

Particle-induced sterile endophthalmitis was observed in a subset of patients who received IVT depot at the end of PPV surgery and was associated with atrophic inferior retinal breaks and RRD in a newly described entity coined “erosive retinopathy.” Given that all eyes had a similar presentation in terms of morphology and timing, the IVT depot was thought to be the cause of the characteristic inferior atrophic retinal breaks. The typical consolidation or layering of Triesence inferiorly postoperatively was situated dependently over the area where retinal breaks developed. Although iatrogenic retinal breaks are a well-known complication of PPV, the characteristic inferior equatorial location of the breaks at the vitreous base and absence of vitreous traction did not indicate a tractional cause and were not located in areas where retinal breaks had been previously associated with any prior retinal detachment in the same eye. Clinical findings were also not typical for infectious endophthalmitis, and cultures and stains were negative for bacteria or fungi in both patients who had vitreous aspirates. Treatment with intravitreal antibiotics also did not prevent the development of retinal breaks and RRD. Thus, erosive retinopathy represents a complex clinical picture of sterile endophthalmitis, inferior atrophic retinal breaks, and associated rhegmatogenous retinal detachment after triamcinolone acetonide injection at the end of PPV.

As we were unable to find other reports in the medical literature, we presume this complication is rare, and the incidence could not be determined by this retrospective review. In all but one case, a partial fluid-air exchange was performed prior to injection of Triesence to facilitate sutureless sclerotomy closure.40 We observed an association between pseudoendophthalmitis and combined phacoemulsification and PPV with MP cases where Triesence was left as a depot injection at the end of PPV.41 In those cases, triamcinolone crystals were observed prolapsed into the anterior chamber, in some cases forming a pseudohypopyon, which over the first postoperative week became accompanied by true inflammatory cell and flare to progress to pseudoendophthalmitis. If anterior chamber prolapse of drug sensitizes the innate immune response, it could explain why this phenomenon of atrophic retinal breaks and RRD has not been reported with office-based IVT injections and why this complication was not observed in cases where a partial fluid-air exchange was not performed and Triesence was injected after sclerotomy closure.42 It remains unknown why pseudoendophthalmitis in the postsurgical setting resulted in atrophic retinal breaks and RRD when this has not been seen associated with cases of office-based pseudoendophthalmitis from Triesence. In fact, IVTA has been studied as a presurgical adjuvant to reduce cytokines that promote proliferative in primary RRD repair and as a postsurgical adjuvant in RRD repair, proliferative diabetic retinopathy, and open globe trauma.30,43,44 Although toxicity studies of triamcinolone acetonide in animals and human cell cultures are conflicting, there is evidence to suggest that contact of large aggregates of triamcinolone acetonide with the retinal surface can create retinal cytotoxicity in a time-dependent fashion, and Triesence formed the largest aggregates in vitro among commercially available forms of triamcinolone acetonide.45–50

Extent of retinal detachment had a strong influence on method of RRD repair and on final visual outcome. Macula-sparing cases manageable by laser retinopexy remained stable over time without need of further intervention for RRD. In those cases, visual outcomes were similar to presurgical expectations excluding pseudoendophthalmitis and RRD. All eyes requiring PPV for RRD repair used long term tamponade with either perfluoropropane or silicone oil. Poor visual outcome at 6 months was common for eyes requiring PPV for RRD repair. Three of the eight patients had poorer vision at last follow-up than prior to initial surgery. Although inflammation is a risk factor for proliferative vitreoretinopathy (PVR), only one eye developed PVR.

There were several limitations to this study, including its retrospective nature, the inability to determine causality or incidence, and the lack of long-term follow-up. The expectation of triamcinolone crystals in the vitreous and/or anterior chamber following Triesence injection at the end of PPV made grading inflammatory cell challenging. If another case is encountered, investigating the vitreous specimen for macrophages engulfing triamcinolone crystals and optical coherence tomography scans through the inferior breaks for evidence of necrosis could elucidate the mechanism of disease. In the cases reported, Triesence was used to treat anticipated postsurgical inflammation and retinal edema associated with PPV/MP. Per the drug label, Triesence is indicated for visualization during vitrectomy and the treatment of sympathetic ophthalmia, temporal arteritis, uveitis, and ocular inflammatory conditions unresponsive to topical corticosteroids. Based upon the limited evidence presented, we recommend following the labeled indications and avoid using IVT depot injection at the end of vitrectomy surgery.

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Patient Demographics

Patient Age (Years) Sex Eye Amount of IVT (mg) Indication for Surgery Primary Procedure Performed Time to Presentation With RD (days) RD Symptomatic at Presentation Macula Status Description of Inferior Retinal Breaks
1 64 F OD 8 RSO/CME SOR/EL/pFAX/IVT 1 No On Two necrotic breaks
2 67 M OS 8 ERM PPV/MP/Capsulotomy/IVT 13 Yes Off Three clock-hour dialysis
3 80 M OD 4 NSC/ERM Phaco/PPV/MP/pFAX/IVT 26 No On Atrophic break
4 73 F OD 4 NSC/ERM Phaco/PPV/MP/EL/pFAX/IVT 30 No On Five atrophic breaks
5 63 F OS 4 ERM PPV/MP/pFAX/IVT 14 Yes On Large atrophic break
6 74 M OD 4 ERM PPV/MP/pFAX/IVT 31 Yes On Large break
7 75 M OS 4 ERM PPV/MP/pFAX/IVT 28 Yes On Two atrophic breaks
8 72 F OD 4 ERM PPV/MP/pFAX/IVT 39 No On Large atrophic break

Surgical Outcomes

Visual Acuity Inflammation Grade Inflammation Grade Post Primary Procedure Post RD Repair
Patient RD Repair Performed Before Primary Procedure Before RD Repair POM1 POM3 POM6 Anatomic Success at 1 Year AC Cell POD1 AC Cell POW1 Vitreous Cell POD1 Vitreous Cell POW1 IOP Preop IOP POD1 IOP POD1 IOP POW1 IOP POM1 IOP POM3 IOP POM6
1 PPV/PFO/EL/SO 20/400 CF@5′ CF@2′ N/A CF@4′ Yes 0.5+ N/A IVT (cell indeterminate) N/A 12 13 15 10 10 N/A 20
2 PPV/PFO/EL/SO 20/40 CF@6′ 20/80 20/70 20/50 Yes 0.5+ 2+ IVT (cell indeterminate) 3+, IVT crystals 10 18 44 13 14 17 16
3 PPV/EL/SO 20/80 20/125 20/100 20/250 20/200 Yes 0.5+ 0 25% air IVT (cell indeterminate) 19 13 26 8 14 18 6
4 PPV/EL/16% C3F8 20/200 20/100 20/400 20/60 20/50 Yes 0.5+ 0.5+ 25% air 2+, IVT crystals 11 15 18 17 13 11 13
5 PPV/EL/SO 20/50 20/50 20/60 20/70 20/125 Yes 2+ 0 VH 2+ (cell indeterminate) IVT crystals 15 14 13 15 15 12 10
6 PPV/EL/SO 20/40 20/60 20/10 N/A 20/20 No* None 0.5+ IVT (cell indeterminate) 2+, IVT crystals 21 17 N/A 16 11 N/A 13
7 Laser retinopexy 20/125 20/40 20/400 20/500 20/70 Yes None 0.5+ 35% air 2+, IVT crystals 16 20 15 18 15 9 8
8 Laser retinopexy 20/70 20/60 20/60 20/60 N/A Yes 1+ 0 IVT (cell indeterminate) IVT (cell indeterminate) 13 11 N/A 12 9 10 N/A
Authors

From Cincinnati Eye Institute, Cincinnati, Ohio (RAS, YPP, REF, MRP); University of Cincinnati Department of Ophthalmology, Cincinnati, Ohio (RAS, YPP, REF, MRP); and Abrahamson Pediatric Eye Institute, Cincinnati Children's Hospital Medical Center, Cincinnati (RAS).

Presented at the Retina Society annual meeting on September 14, 2018 in San Francisco, CA.

The authors report no relevant financial disclosures.

Address correspondence to Robert A. Sisk, MD, FACS, Cincinnati Eye Institute, 1945 CEI Drive, Cincinnati, OH 45242; email: rsisk@cincinnatieye.com.

Received: August 14, 2018
Accepted: March 11, 2019

10.3928/23258160-20191009-03

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