Posterior sub-Tenon triamcinolone injection in the treatment of postoperative cystoid macular edema secondary to pars plana vitrectomy

Abstract

Purpose:

To evaluate the efficacy and safety of posterior sub-Tenon triamcinolone (PSTA) in chronic postoperative cystoid macular edema (PCME) after pars plana vitrectomy (PPV).

Methods:

Consecutive 22 patients who developed chronic PCME after PPV and underwent PSTA treatment were included in this retrospective study. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were measured pre injection and post injection at one month, three months, six months, and at last visit. The patients were divided into three groups according to the injection response status: complete, partial, and resistant.

Results:

The mean follow-up period was 26.4 ± 16.2 months after PSTA. According to pre-injection values, there was a significant improvement in the values of BCVA and CMT at the first, third, and sixth months and at the last examination (P < 0.05). In the final examination, PCME recovered completely in 12 patients, partially in 8 patients, and resistance was observed in 2 patients.

Conclusion:

Posterior sub-Tenon triamcinolone seems to be effective in chronic PCME following PPV.

Postoperative cystoid macular edema (PCME) is a vital pathology that can be seen after vitreoretinal surgery, like other ocular surgeries, and delays visual rehabilitation in the postoperative period.[1,2] In addition to the thought that inflammation plays a vital role in its pathogenesis, many factors are held responsible. Some accompanying diseases, regardless of vitreoretinal surgery, can also cause thickening, cystic changes, and edema in the retina; therefore, the actual detection rate of this entity is not easy.

Various treatment options, such as steroid and anti-vascular growth factor (anti-VEGF) administration via intravitreal, sub-Tenon, and suprachoroidal have been discussed in many studies, and very different success rates have been reported in the treatment of PCME that develops secondary to various ocular surgery.[3–5] There are not many studies in the literature on the frequency, risk factors, and treatment of PCME secondary to vitreoretinal surgery. Intravitreal dexamethasone and anti-VEGF have been previously used for treatment and successful results have been reported.[2,3–8]

Structural changes occur in eyes that have undergone vitrectomy. Accordingly, the pharmacokinetics of some drugs changes and the half-life are shortened in vitrectomized eyes compared to non-vitrectomized eyes.[9] However, posterior subtenon injection of triamcinolone can provide comparable efficacy and duration of action in both vitrectomized and non-vitrectomized eyes.[9,10] Posterior sub-Tenon triamcinolone (PSTA) should also be considered as an advantageous option because it is not injected into the eye. Intravitreal application of triamcinolone has the risk of complications such as endophthalmitis, pseudoendophthalmitis, iatrogenic crystalline lens injury, and retinal detachment; by sub-Tenon administration, these complication risks are eliminated.[11] To avoid the risks of intravitreal administration, the efficacy of suprachoroidal administration in treating PCME has also been reported.[3] Moreover, triamcinolone acetonide is more cost-effective and is one of the few treatment options with sufficient and long-lasting efficacy in vitrectomized eyes.[9]

Our aim in this study was to investigate the efficacy and safety of PSTA treatment in PCME after vitreoretinal surgery, which has been proven effective in treating various ophthalmic diseases and PCME following cataract surgery.

Methods

This retrospective study enrolled patients who underwent a PSTA injection for refractory PCME after vitreoretinal surgery. The study was conducted at the university hospital. The study was approved by the local ethics committee and followed the tenets of the Declaration of Helsinki.

All medical records, including case sheets, optical coherence tomography (OCT), and fundus fluorescein angiography (FFA) digital image database, of the patients who received the injection for PCME refractory to medical treatment between July 2015 and March 2019 were analyzed. Refractory PCME was defined as a presentation of retinal thickening accompanied by intraretinal cysts in OCT examination for at least six months despite at least one previous treatment of non-steroidal anti-inflammatory drugs (NSAID) eye drops and/or oral acetazolamide.

Patients who had undergone intraocular surgery six months before pars plana vitrectomy (PPV), who had anterior segment procedures combined with PPV, and who had a history of uveitis, retinal vascular pathology, and ocular trauma were excluded. Furthermore, patients who received medical treatment and had systemic problems that might cause macular edema, and epiretinal membrane (ERM) formation following PPV before PSTA injection were excluded from the study. Pediatric cases were also excluded. Furthermore, cases with degenerative cystic changes in the inner nuclear layer observed in the internal limiting membrane (ILM) peeled vitreoretinal interface disorder patients were not considered PCME and not included in the study.[12]

Age, sex, right-left eye, lens status (phakic-pseudophakic), indication of PPV, cases of ILM peeling performed in PPV, and the time between PPV and PCME diagnosis were determined. A Snellen chart assessed the best-corrected visual acuity (BCVA) and converted it to logMAR values for statistical purposes.

The central macular thickness (CMT) was analyzed by spectral-domain OCT (SDOCT) (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany) using averaged multiple B-scans passing through the central point of the fovea. The centering, accuracy of automated segmentation, and signal quality of the scan were evaluated while reviewing OCT images. FFA was performed at the physician’s discretion and it determined leakage. Triamcinolone acetonide (Kenacort, Bristol-Myers Squibb, Sermoneta, Italy) was administered in the minor operating room to the posterior sub-Tenon area at a volume of 0.5 ml at a dose of 40 mg/ml.

The BCVA and CMT values at the first, third, and sixth month and last examination were statistically compared. Intraocular pressure (IOP) values were measured at each examination, and cases with high pressure or glaucoma medications initiated and all complications after injection were recorded. Additional injections and the need for cataract surgery were recorded.

Treatment response was defined as complete recovery (patients with the foveal contour formation and the complete removal of edema after injection), partial recovery (patients with a significant reduction [at least 10%] in thickness but the incomplete removal of edema and without the foveal contour formation), and resistance (cases with no change in CMT).

Patients, who responded partially to the treatment by showing a significant decrease in macular edema after the first injection underwent reinjection if the progression of recovery stopped and if this was determined by a comparison of OCT images at two consecutive visits. Furthermore, the PSTA injection was repeated in the case of recurrence in patients who responded to the first injection with the complete recovery of macular edema. There was at least three months between repeat injections.

Statistical analysis

Statistical analysis was performed using the Statistical Package for the Social Sciences software (version 22; SPSS, Chicago, IL). Quantitative data were presented as mean ± standard deviation. Friedman test was used to compare measured parameters pre-injection and at one month, three months, six months, and at last visit after PSTA injection. Wilcoxon test with Bonferroni correction was used for binary comparisons. Significance was assessed at the levels of P < 0.05.

Results

Twenty-two eyes of 22 patients (15 males, 7 females) who underwent the PSTA injection for PCME after vitreoretinal surgery were included in the study. The mean age of the patients was 62.7 ± 8.7 (range 40–75) years. The mean follow-up period was 26.4 ± 16.2 (range: 6–59) months after PSTA. The patients’ pre-injection baseline characteristics and post-injection data are presented in Table 1 (age, sex, right-left eye, diagnosis [the cause of PPV], the time between PPV and PCME diagnosis, lens status [phakic-pseudophakic], patients with ILM peeling during PPV, follow-up time, the pre-injection and the last visit BCVA, CMT, IOP, and response status).

Table 1.

The patients’ baseline characteristics, post-injection last visit data, and response status

	Age (years)	Sex	Side	Cause of PPV	Time between PPV-PCME (month)	Time between PPV-PSTA (month)	Lens Status	ILM Peeling During PPV	Follow-up Time (month)	BCVA Preop. (LogMAR)	CMT Preop (µm)	IOP Preop (mmHg)	BCVA Last Visit (LogMAR)	CMT Last Visit (µm)	IOP Last Visit (mmHg)	Resolution of PCME after PSTA
1	60	F	R	Endophthalmitis	31	37	PCIOL	-	51	1.80	549	22	1.30	263	12	complete
2	56	M	L	RD	36	42	PCIOL	-	41	0.70	659	8	0.40	274	11	complete
3	67	M	R	VMT	12	18	PHAKIC	+	29	0.70	693	14	0.30	381	14	complete
4	40	M	R	RD	7	14	PCIOL	-	26	0.70	709	16	0.52	313	18	complete
5	59	F	R	RD	9	15	PCIOL	-	26	1.51	492	11	1.00	386	12	complete
6	68	F	R	VMT	22	28	PHAKIC	-	27	0.40	303	14	0.40	241	14	complete
7	74	M	R	RD	35	41	PCIOL		12	0.70	381	15	1.00	326	10	complete
8	75	M	R	ERM	4	10	PCİOL	-	11	0.30	425	13	0.30	325	11	complete
9	55	M	R	RD	6	12	PCIOL	+	7	1.00	690	17	1.00	341	14	complete
10	64	M	R	Nucleus drop	4	10	PCIOL	-	7	0.40	548	8	0.05	315	15	complete
11	69	M	R	RD	3	9	PHAKIC	-	6	1.30	571	10	1.30	353	8	complete
12	71	M	R	RD	47	53	PCIOL	+	59	0.70	423	17	0.30	424	17	partial
13	75	F	L	ERM	5	11	PHAKIC	-	48	1.30	553	14	1.00	477	14	partial
14	61	F	L	MH	3	9	PCIOL	+	30	1.30	392	9	1.30	270	17	partial
15	56	M	L	RD	28	34	PCIOL	-	28	1.80	674	15	1.30	214	19	partial
16	67	F	L	RD	24	30	PCİOL	-	23	1.30	354	16	0.70	308	15	partial
17	59	M	R	RD	9	16	PHAKIC		19	1.30	592	21	1.00	336	10	partial
18	66	M	L	Nucleus drop	7	15	PCIOL	-	12	1.00	520	16	0.70	459	16	partial
19	65	M	R	IOL dislocation	2	8	PCIOL	-	6	0.70	651	18	0.52	340	18	partial
20	52	M	L	IOH	40	46	PCIOL	-	55	1.51	405	18	0.52	275	10	resistance
21	61	F	L	ERM	3	10	PCIOL	-	27	1.00	399	14	0.15	382	14	resistance
22	64	M	R	RD	8	14	PCIOL	-	12	1.00	393	7	1.00	435	7	resistance

PPV; pars plana vitrectomy, PCME; postoperative cystoid macular edema, ILM; internal limiting membrane, BCVA; best-corrected visual acuity, CMT; central macular thickness, IOP; intraocular pressure, PSTA; posterior subtenon triamcinolone acetonide, M;male, F;female, R;right, L;left, RD; retinal detachment ,IOH;intraocular hemorrhage, ERM; epiretinal membrane, IOL; intraocular lens, MH; macular hole, VMT; vitreomacular traction, PCIOL;posterior chamber intraocular lens

In four (18%) of the 22 patients, the ILM was peeled during the operation [Table 1]. All eyes had normal foveal anatomy after PPV, and the PCME occurred with a time delay. None of the patients had phacoemulsification with PPV, and none of the patients underwent any intervention between vitrectomy and PSTA injection. The time between the pars plana vitrectomy and the detection of macular edema was 2 to 47 months (mean ± SD: 15.6 ± 14.3). Seventeen patients were pseudophakic, and five patients were phakic at the first PSTA injection. During the follow-up period, one patient underwent cataract surgery. IOP change was not statistically significant [Table 2]. IOP increased to 25 mmHg at the third month after injection in one patient and was controlled by medical treatment.

Table 2.

The mean BCVA, CMT, and IOP values and statistical analysis of the patients’ data

	Pre-injection	Post-Injection 1 month	Post Injection 3 months	Post Injection 6 months	Last Visit	P
Best-corrected visual acuity (logMAR)	1.01±0.43	0.90±0.45	0.98±0.43	0.82±0.49	0.73±0.40	<0.001*
		0.022†	0.13†	0.01†	0.001†
Central macular thickness (µm)	517±126	367±114	366±100	360±104	361±76	0.002*
		0.001†	0.005†	0.008†	<0.001†
Intraocular pressure (mmHg)	14.2±4.0	14.3±3.5	13.3±2.9	15.3±4.8	13.4±3.3	0.24*

*Friedman Test. ^†Pairwise comparison (pre-injection and follow-up visit) Wilcoxon test with Bonferroni correction. (<0.01 statistically significant level)

The improvement in BCVA and CMT was statistically significant [Table 2]. Post-injection CMT was significantly less at all time points compared to pre-injection. When the patients were evaluated according to the response status after the first PSTA injection, complete recovery was seen in 11 patients, partial recovery in 8 patients, and resistance to treatment in 3 patients. The OCT image of one patient who had complete recovery is shown in Fig. 1. During the follow-up period, seven patients received one additional dose of PSTA, and one patient received three additional doses of PSTA. At the last visit, 12 patients had complete recovery, 8 had residual cystoid macular edema, and 2 had resistance. A mild ERM developed in two patients in the follow-up period following the PSTA injection.

Figure 1.

(a) OCT images of the patient before sub-Tenon triamcinolone injection. (b) Post-injection 1^st month OCT image after complete recovery. (c) Post-injection 6^th month OCT image. (d) Post-injection 12^th month OCT image shows that complete recovery of cystoid macular edema continues

Discussion

Posterior sub-Tenon injection of triamcinolone is an effective treatment modality for postoperative cystoid macular edema following vitreoretinal surgery. Eighty-six percent of cases responded positively to triamcinolone injection but repeated injections are needed in some cases.

Postoperative cystoid macular edema after vitreoretinal surgery is a significant cause of visual impairment, but there are not much data about its frequency, chronicity rate, and treatment. Its pathogenesis is thought to be multifactorial, similar to PCME after other eye surgeries, but inflammation is considered to play the primary role in it. The most important effect of inflammation is increasing vascular permeability by affecting the blood–retinal barrier.[13] Kim et al.[1] evaluated postoperative inflammation on the first day after PPV and found a correlation between the rate of inflammation and PCME that occurred one month later. The diameter of the instruments used in vitreoretinal surgery, the amount of macular dye used, and the use of a perioperative endolaser were considered to be factors that stimulate the inflammatory reaction in the macula.[12,14,15] Moreover, phototoxicity and the duration of surgery may play a role in the development of PCME after PPV. The age of the patient is also a factor, and it has been reported that as age increases the probability of PCME increases after surgery for vitreoretinal pathologies.[15,16]

Currently, it is not known clearly what similarities and differences the PCME observed after PPV has, in terms of progression, with the PCME observed after other intraocular surgeries. The selection of surgery included is very heterogeneous in our study. Still, we report that we did not include vascular diseases and that none of the patients had preoperative macular fluid accumulation. The spontaneous resolution of PCME after cataract surgery occurs in 90% of patients, even if it takes more than one year.[17,18] However, it is not known exactly how much of this ratio is observed in PCME after vitrectomy. It is thought that PCME observed after PPV is less likely to resolve spontaneously, is more resistant to treatment, and more likely to relapse.[2] In contrast, PPV has been reported to be effective in the treatment of PCME after cataract surgery.[19,20] In the present study, PCME was detected at an average of 15.6 months (range: 2–47) after vitrectomy. Similar to our study, Alam et al.,[2] who investigated PCME after vitrectomy, detected it five months (range 3–12 months) after vitrectomy, which is a period shorter and different from ours. However, the time for the occurrence of PCME after PPV was longer in both studies compared to pseudophakic CME; it was reported that pseudophakic CME also may be delayed or very late onset.[21,22] The PCME following PPV may have occurred more delayed than pseudophakic CME due to altered anatomy and physiology with vitreoretinal surgery. Patients have benefited from steroid treatment, although the underlying cause and role of inflammation are controversial in late-onset PCME cases. The frequency of PCME after PPV has been reported at different rates. Frisina et al.[14] found the prevalence of PCME to be 12.8% in cases with idiopathic ERM, Kim et al.[1] found 47% cases including diabetic patients, and Staudt et al.[23] presented angiographic leakage in 66.7% of cases with macular hole after PPV. To determine the true rate of PCME after vitreoretinal surgery, it has been argued that vitrectomy should be considered for vitreous floaters without any other retinal pathology.[24] De Nie et al.[25] detected postoperative CME in six (5%) of 110 patients who had undergone PPV for vitreous floaters and four of these patients were treated with topical drops, while two patients were resistant to treatment. It is also expected that there will be less inflammation and edema in more limited surgeries.

In general, it is recommended that oral acetazolamide and topical NSAIDs should be the first-line treatment for postoperative CME. If there is no response, it is recommended to switch to injection treatment, which is more invasive.[6] An intravitreal dexamethasone is a steroid option that has been reported to be used in PCME after vitrectomy and to be effective.[6] In intravitreal dexamethasone treatment, as in other steroid treatments, relapses can also be observed after three months, and although its effectiveness decreases slightly the CMT and visual acuity do not return to pre-treatment values at the end of the sixth month.[6] Intravitreal anti-VEGF treatment has been tried in PCME after vitrectomy but has not been found to be effective.[2,8]

Triamcinolone acetonide is another steroid option in the treatment of PCME after vitrectomy. Some studies have reported successful results with intravitreal triamcinolone acetonide injection in pseudophakic CME.[26,27] Satisfactory results have also been reported in the case of sub-Tenon steroid treatment.[28] Alam et al.[2] reported the use of triamcinolone in one study to treat 36 cases with refractory PCME after vitrectomy, and intravitreal administration was preferred in that study. To the best of our knowledge, there is no study in the literature on the sub-Tenon application of triamcinolone for refractory PCME after PPV, as in the current study. The study conducted by Alam et al.[2] included vitreomacular interface disorder patients without vascular pathology. Although it is not identical, the current study—with which we compared our results—bears the highest similarity to our study. Similar to our study, CMT was significantly reduced after injections in their study. Alam et al. observed a significant increase in visual acuity at one month following triamcinolone injection in PCME after vitreoretinal surgery. However, they reported that a statistically significant increase did not persist at 3, 6, and 12 months. The change in BCVA significantly increased when we evaluated all visits, and this improvement remained significant between pre injection and last visit in pairwise comparison in our study. Contrary to what was shown in his study, the increase in BCVA continued over time in our study.

Alam et al. required additional intravitreal bevacizumab therapy in eleven (30%) of the patients treated with triamcinolone within a one-year follow-up period and did not respond to treatment. Likewise, during the follow-up period we applied additional sub-Tenon steroid treatment to 30% (eight patients) of patients. Furthermore, one patient in our study and two patients in the study conducted by Alam et al. showed transient IOP elevation requiring antiglaucomatous use.

The cataract surgery combined with PPV increases the rate of PCME in the postoperative period.[23,29] We did not include cases with PPV combined with cataract to investigate the treatment of PCME caused by vitrectomy alone. However, several studies did not find a difference in the incidence of postoperative CME in phakic and pseudophakic patients undergoing PPV.[14,15] ILM peeling is still a controversial issue in vitreoretinal surgery. In our study, four patients had undergone ILM peeling during vitrectomy. It has been reported that degenerative ellipsoid cystic changes occur at the level of the inner nuclear layer in the late stage in cases of ILM peeling during ERM surgery.[12] The mechanism of these cystic changes is thought to damage the Müller cells, unlike PCME.

The limitations of the present study are its retrospective design, a small number of patients, and the absence of a control group.

Conclusion

The most crucial advantage of sub-Tenon triamcinolone injection over intravitreal injections is that it is a cost-effective and less invasive procedure. It eliminates many complications such as retinal detachment and endophthalmitis brought by intraocular applications. An essential advantage of its being applied to the posterior sub-Tenon’s space in vitrectomized eyes is that it is less affected by the increased clearance rate. In the present study, we evaluated refractory PCME to medical treatment after vitreoretinal surgery and observed that the effectiveness of PSTA implementation was comparable to other methods. Larger comparative studies evaluating PCME treatment after vitrectomy are needed to confirm the results of this study.

Ethics approval

Ethical approval was obtained from the institution’s ethics committee on non-pharmacological clinical research (Okmeydani Training and Research Hospital, 2020-81).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.