C A S E R E P O R T
Intravitreal triamcinolone acetonide for the management
of papillophlebitis and associated macular edema
Yo-Chen Chang Æ Wen-Chuan Wu
Received: 11 February 2007 / Accepted: 11 July 2007 / Published online: 16 August 2007
Ó Springer Science+Business Media B.V. 2007
Abstract Background To investigate the efficacy of intravitreal injection of triamcinolone acetonide in the management of papillophlebitis and associated cystoid macular edema. Methods This study was a retrospective medical records review of four eyes of four patients (three males and one female) who had approximately 2–4 months history of papillophlebitis and associated persistent cystoid macular edema. These patients were treated with a single intravitreal injection of 4 mg triamcinolone acetonide. Mean follow-up time was 15 ± 4 months. The outcome measures included best corrected visual acuity (BCVA), intraocular pressure (IOP), and central retinal thickness by optical coherence tomography (OCT). Results The BCVA ranged from 20/100 to 20/ 60 pre-operation. The mean gain in BCVA was 7 ± 1 Snellen lines. All eyes had BCVA of 20/20 at the last visit. The mean baseline central retinal thickness as measured by OCT was 529 ± 53 lm. The mean central retinal thickness by OCT was 235 ± 15 lm at 1-week follow-up examination. At the last visit the
mean central retinal thickness by OCT was 161 ± 7 lm. One patient experienced an increase in IOP after the first injection and another patient had IOP elevation after the second injection. Both were well controlled with single topical anti-glaucoma medication. Conclusion Intravitreal injection of tri-amcinolone acetonide appears to be an effective treatment for patients with papillophlebitis and asso-ciated cystoid macular edema.
Keywords Cystoid macular edema Intravitreal injection Papillophlebitis Triamcinolone acetonide
Introduction
Papillophlebitis is an uncommon ophthalmologic condition of obscure etiology. Unlike classic central retinal vein occlusion (CRVO), patients suffering from this disease are usually healthy and younger than 50 years of age [1]. Most patients complain of blurred vision or photopsia. Typical ophthalmologic findings include unilateral optic disc edema, dilata-tion, and tortuosity of the major retinal veins with a variable amount of retinal hemorrhage [2,3]. Tradi-tional treatment for papillophlebitis includes systemic and periocular steroid therapy, platelet inhibitors or anticoagulation. However, the effect is controversial [4]. Intravitreal triamcinolone acetonide has increas-ingly been used for the treatment of diabetic macular Y.-C. Chang
Department of Ophthalmology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
W.-C. Wu (&)
Department of Ophthalmology, Kaohsiung Medical University, No.100, Zihyou 1st Rd, Kaohsiung 807, Taiwan
e-mail: [email protected] DOI 10.1007/s10792-007-9128-8
edema [5], neovascular glaucoma [6], retinal vein occlusion [7], chronic uveitis [8], and other clinical situations. The safety and efficacy of intravitreal triamcinolone acetonide have been well studied in animal models [9]. The purpose of this study was to evaluate the efficacy of intravitreal triamcinolone acetonide in the management of papillophlebitis and secondary cystoid macular edema.
Materials and methods
This study was designed as a retrospective medical records review. Between May 2004 and July 2005, patients with papillophlebitis were considered for enrollment in the study. Table1 summarizes the inclusion criteria. Patients underwent clinical exam-ination including the Snellen visual acuity test, intraocular pressure (IOP) measurement, slitlamp inspection of the anterior segment, dilated fundus examination with indirect ophthalmoscopy, fluores-cein angiography (FAG), and optical coherence tomography (OCT-3, Carl Zeiss Meditec, Dublin, CA, USA) prior to the injection of triamcinolone acetonide (40 mg mL 1 Kenacort-A, Bristol-Myers Squibb). These four patients also received biochem-ical examinations for complete blood count (CBC), serum cholesterol, triglyceride, blood sugar, erythro-cyte sedimentation rate (ESR), C-reactive protein (CRP), venereal disease research laboratory (VDRL), rheumatoid factor (RhF), and antinuclear antibody (ANA). All patients were observed for at least 2 months prior to undergoing this investigative treatment.
All patients gave written informed consent before intravitreal injection. All injections were carried out under sterile conditions in an operation room by a vitreoretinal surgeon. Topical (0.5%) proparacaine hydrochloride (Alcaine; Alcon) was used for anes-thesia. Four milligrams (0.1 mL) of crystalline triamcinolone acetonide—without prior removal of the vehicle—was injected into the vitreous cavity by
using a 27-gauge needle through the temporal upper pars plana, 4 mm from the corneal limbus. Post-operation, gentamycin eye drops were applied four times daily for one week.
Patients underwent postoperative follow-up with repeated clinical examination including Snellen visual acuity test, IOP measurement, dilated fundus examination, and OCT.
Results
The baseline and follow-up patient data are included in Table 2. There were three males and one female. The mean age of patients was 40 ± 11 years (range: 24–50 years). The biochemical examinations of these four patients were all unremarkable. The mean duration of symptoms before treatment was 3 ± 1 months (range: 2–4 months). The range of pre-operation best corrected visual acuity (BCVA) was 20/100–20/60. All eyes showed significant improvement on BCVA one week after treatment. Three out of four eyes (75%) had BCVA of 20/20 at 1 month post-operation. All four patients were fol-lowed up for at least 12 months (range: 12– 20 months). Only case 1, with recurrent cystoid macular edema and a decrease in BCVA 6 months after treatment, received a second injection of triamcinolone acetonide, which led to better visual improvement than the first treatment course. During the follow-up period, the increase in visual acuity was stable in all four eyes.
All eyes had a significant reduction in central retinal thickness as demonstrated by OCT (Table3). The mean central retinal thickness was 529 ± 53 lm pre-operation, and all eyes (3/3) had the thickness back to normal range at one month post-operation. Thereafter, the thickness showed no significant change at each time point. At the last follow-up, the mean central thickness was 161 ± 7 lm (range: 152– 168 lm).
Table 1 Inclusion criteria
* Age cannot be older than 50 years
* Without systemic vascular disease or other systemic conditions (hypertension, diabetes, hyperlipidemia, and platelet abnormalities) * Typical fundus finding of unilateral optic disc edema, dilatation, and tortuosity of the major retinal veins with a variable amount of
The baseline and follow-up IOP are summarized in Table 4. After the first injection of triamcinolone acetonide, only one eye (case 4) developed IOP values of 22 mmHg or more and responded to single topical anti-glaucoma medication. In this case, the IOP maintained at baseline level after discontinuing anti-glaucoma medication for 4 months. Case 1 received a second injection of triamcinolone aceto-nide and the IOP increased to 25 mmHg two months after treatment. The IOP was well controlled by single topical anti-glaucoma medication and the medication was able to be discontinued over the course of follow-up. There was no difference between the baseline (15.5 ± 3.8 mmHg) and the last follow-up (16.0 ± 2.4 mmHg) in intraocular pressure (p = 0.66).
With the exception of IOP elevation, no other operation-related complications such as endoph-thalmitis, cataract, or retinal detachment were encountered.
Figure1is an illustrative case (case 3) that showed a good anatomical and functional response to treat-ment. This is a 39-year-old, otherwise healthy man who had sudden onset of blurred vision in his left eye for a duration of 4 months. His medical and ophthal-mological history was unremarkable. Fundoscopy of the left eye showed venous tortuous and engorge-ment, congested optic disc edema, flame-shaped hemorrhages, and nerve fiber layer hemorrhages in the posterior pole (Fig.1A). No abnormalities were found in the right eye. FAG showed significant disc edema and macular edema. There was no obvious retinal ischemia or neovascularization (Fig.1B). OCT measured a central macular thickness of 468 lm in the left eye (Fig.1C). One month after injection, the patient’s BCVA in the left eye improved to 20/20. Fundoscopic examination showed a dramatic resolution in disc edema, hemorrhage, venous dilatation, and tortuosity (Fig. 1D). FAG showed almost complete resolution of optic disc edema and cystoid macular edema (Fig. 1E). The central macular measured by OCT also showed a dramatic decrease to 160 lm (Fig. 1F).
Discussion
There is currently no proven effective treatment for papillophlebitis and associated cystoid macular
Table 2 Summary of baseline and follow-up best-corrected visual acuity for four patients treated with intravitreal injection of triamcinolone acetonide No/Sex/Age Duration Baseline 1 w 1 m 2 m 4 m 6 m 8 m 10 m 1 2 m 14 m 1 6 m 18m Line gain Time to recurrence Re-injection 1/M/50 y 2 m 20/100 20/40 20/40 20/30 20/30 20/100 20/20 20/20 20/20 20/20 20/20 20/20 8 6 m Y 2/M/45 y 3 m 20/100 20/30 20/20 20/25 20/20 20/20 20/20 20/20 20/20 20/20 20/20 N/A 8 N/A N 3/M/39 y 4 m 20/60 20/30 20/20 20/20 20/20 20/20 20/20 20/20 20/20 N/A N/A N/A 6 N/A N 4/F/24 y 3 m 20/70 20/25 20/20 20/20 20/20 20/20 20/20 20/20 20/20 N/A N/A N/A 7 N/A N
edema. Reviewing previous studies, a slow, sponta-neous resolution over a 3 to 6 month period in papillophlebitis has been reported [1,2,10,11]. Fong et al. reported that 54% of patients observed for at least 6 months had acuity of 20/40 or better at the time of the final examination [4]. However, some authors have shown some cases to have poor visual outcome, and present visual acuity does not appear to
be predictive of visual or anatomic outcome [12]. Recchia et al. found that 40% of patients had final visual acuity of 20/200 or worse [12]. Frucht et al. reported that 55% of patients had visual acuity of counting finger or worse [13].
In this study, intravitreal triamcinolone acetonide was effective in improving visual acuity and reducing the degree of cystoid macular edema in patients with
Table 3 Summary of baseline and follow-up central retinal thickness (lm) from optical coherence tomography
No Initial 1 w 1 m 2 m 4 m 6 m 8 m 10 m 12 m 14 m 16 m 18 m 20 m
1a N/A N/A N/A N/A N/A 462 162 170 162 168 170 165 168
2 556 236 160 165 164 163 165 161 164 160 162 N/A N/A
3 468 220 160 150 152 155 151 156 152 N/A N/A N/A N/A
4 562 250 165 160 165 163 166 162 161 N/A N/A N/A N/A
a Case 1 first visited our clinic in May 2004, which was 6 months earlier than the acquisition of OCT in our department
Table 4 Summary of baseline and follow-up intraocular pressure (mmHg)
No Initial 1 w 1 m 2 m 4 m 6 m 8 m 10 m 12 m 14 m 16 m 18 m 20 m
1 15 16 16 15 16 16 25 17 16 18 15 19 16
2 13 14 18 19 13 14 14 15 14 16 13 N/A N/A
3 13 18 18 17 17 15 14 14 16 N/A N/A N/A N/A
4 21 23 25 23 21 20 20 20 19 N/A N/A N/A N/A
Fig. 1 Patient 3. (A) Pre-operation fundus photograph shows
prominent congested disc edema, flame-shape hemorrhage in four quadrants, cotton wool spots, and tortuous retinal veins. (B) Late phase of fluorescein angiography performed before therapy showed cystoid macular edema. (C) Optical coherence tomo-gram taken before therapy also showed prominent macular
edema. (D) One month after triamcinolone acetonide injection, there were marked resolution of disc edema and flame-shape hemorrhage. (E) In the late phase of fluorescein angiography, no obvious cystoid macular edema was observed. (F) Optical coherence tomogram taken 1 month after injection. The visual acuity improved along with resolution of macular edema
papillophlebitis. The improvement in visual acuity was very dramatic: All four eyes had BCVA of 20/20 at the last visit. And the improvement in visual acuity was maintained for at least 12 months after treatment. The mean final visual gain was 7 ± 1 Snellen lines, which was very impressive. According to previous reports, patients with incomplete CRVO and good vision (20/200) often do quite well without treatment [1,2,10,11]. However, the associated CME usually takes several months to resolve, and the functional damage is sometimes irreversible. Intravitreal triam-cinolone acetonide can markedly improve the inflammation of the retinal vein and rapidly resolve the CME.
In patients with classic CRVO and associated cystoid macular edema, the improvement in visual acuity after injection with triamcinolone acetonide was not as effective as papillophlebitis. Cekic et al reported the mean final visual gain was 1.3 Snellen lines for a mean follow-up of 10 months [14]. Ip et al. found the mean gain in visual acuity was 2.2 Snellen lines at the 6-month follow-up [7].
Recurrent cystoid macular edema with a concom-itant reduction in visual acuity only occurred in one of four patients (25%) at the 6-month follow-up examination. In classic CRVO, the rate of recurrent cystoid macular edema was much higher. Williamson et al. reported 67% of patients with CRVO encoun-tered recurrent cystoid macular edema after injection of triamcinolone acetonide [15]. And, disappoint-ingly, even repeated injections did not prevent deterioration in visual acuity at 12 months [15]. Cekic et al. found 10 of 24 eyes had recurrent cystoid macular edema after injection of triamcinolone acetonide [14]. A possible explanation of this finding might be the different etiology and pathogenesis of these two diseases. In papillophlebitis it might result from a phlebitis of major retinal veins surrounding the optic nerve. The inflammation promotes venous thrombosis, which produces papilledema [16]. How-ever, the possible pathogenesis of CVRO might be the obstruction of the scleral outlet, which leads to ‘‘compartment syndrome’’ and thus results in persis-tent retinal hypoxia [17]. Although the mechanism of triamcinolone acetonide inducing resolution of papil-lophlebitis and associated cystoid macular edema is not well understood, it is probably due to the potent anti-inflammation character and the ability to reduce the breakdown of the blood-retina barrier [18].
However, in patients with CRVO, intravitreal triam-cinolone acetonide can transiently reverse cystoid macular edema, but may need another method to restore blood flow and hypoxic condition. And radial optic neurotomy may be a method for inducing collateral formation to restore blood flow [17,19].
In conclusion, intravitreal injection of triamcino-lone acetonide may be a safe and effective treatment for papillophlebitis and associated cystoid macular edema and achieve rapid improvement in visual acuity. The effect seemed to be long-lasting. How-ever, the main shortcoming of this study was a small sample size. Larger prospective studies are necessary to better ascertain the benefit of intravitreal triam-cinolone acetonide in the management of papillophlebitis.
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