Ten-Year Follow-Up of Orbital Volume Augmentation With Calcium Hydroxyapatite Filler in Postenucleation Socket Syndrome

Abstract

Purpose:

To describe the efficacy and persistence of injectable calcium hydroxyapatite (CAHY) to correct orbital volume deficit in postenucleation socket syndrome.

Methods:

An observational study was conducted as a clinical review of all patients in the authors' practice who received injectable CAHY placed in the extraconal and intraconal space to increase orbital volume with a 10-year follow up. The amount of CAHY to be injected was defined according to the degree of orbital volume deficit. Patients previously treated with radiotherapy or with a conjunctival fornix insufficient to accommodate the external prosthesis were excluded. All the patients with at least 10 years of follow up were included in the study.

Results:

Thirty-one postenucleation socket syndrome patients received injectable CAHY for orbital volume augmentation, with a 10-year follow up. The mean amount of preoperative relative enophthalmos measured by Hertel’s exophthalmometry was 14.16 ± 2.15. An increase in the mean orbital volume of 3.35 ± 0.91 at 6 months and 2.97 ± 1.35 at 10 years was obtained. The mean follow-up was 219 ± 18 months (range, 184–240). Patients demonstrated clinical and cosmetic improvement that was observed to continue for 10 years. The complications were peribulbar ecchymosis, 2 extrusions of the internal prosthesis, and 2 ptosis.

Conclusions:

Injectable CAHY provides safe, simple, repeatable, and cost-effective technique to treat volume deficiency in the enophthalmic orbit in the long term. The volume augmentation obtained with this semipermanent filler demonstrated a lasting effect in the orbit with negligible loss of volume at 10 years.

Injectable calcium hydroxyapatite can provide a long-term volume augmentation solution for anophthalmic cavity.

Postenucleation socket syndrome (PESS) is a clinical entity with a reduced volume of the orbital contents, which can arise after enucleation or evisceration of the eye.^1–3 Patients usually present with enophthalmos, ptosis, anomalies of the upper eyelid fold, malposition of the lower eyelid, and difficulty in wearing external prosthesis.

The subsequent orbital volume deficit can be corrected by 2 nonexclusive ways: either by increasing the volume of the external prosthesis or by increasing intraorbital volume by placing a bigger internal prosthesis or a dermo-adipose graft.³ Both methods alone cannot totally compensate for the volume loss as external prostheses need to be small enough to be contained in the fornices, and intraorbital implants should not be too large to be covered by the conjunctiva.^4,5

Different substances such as cross-linked collagen, silicone oil, autologous fat, hydrogel pellet expanders, hyaluronic acid, and polyacrylamide gel have been used for injection into the intraorbital space. These have a short half-life, give unpredictable volume recovery, inflammatory reactions, material migration, and extrusion.^6–11

To be able to correct the volume deficit of the orbit in patients with PESS without significant fibrotic phenomena due to radiotherapy or repeated traumatic episodes, we have been injecting fillers since 2005 as the injection is a minimally invasive procedure, the administration technique is easy, and it gives an immediate, predictable, and repeatable result.¹² Furthermore, patient discomfort is usually minimal, recovery is quick, and there is no need for a new prosthesis nor general anesthesia.^13–18

Among all the available substances, calcium hydroxyapatite (CAHY) is a semisolid filler that has received Drug Administration’s approval for various functional and cosmetic purposes.¹⁹ It consists of 30% CAHY particles (25–45 μm size range), 70% glycerin, sodium carboxymethylcellulose, and water. CAHY was first introduced as a filler in dentistry and then applied to oculoplastic surgery.^20–23

We hereby report our favorable experience in the treatment of PESS with a single, off-label injection of CAHY in patients with at least 10 years of follow up. All images from the patients were published after gaining a signed consent.

METHODS

Patients were treated and enrolled by the Oculoplastic Unit at the Department of Ophthalmology of IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy from January 2005 to September 2015. The study was compliant with the Health Insurance Portability and Accountability Act and in accordance with the principles outlined in the Declaration of Helsinki (2013). Consent has been obtained from the patient for publication of the medical photography included in the article. The study was approved by the Institutional Review Board.

For patients to be included in the study, they had to show PESS secondary to enucleation or evisceration performed for a traumatic event. Initial indications for enucleation were trauma (20; 64.52%), sore blind eye from retinal surgery (4; 12.90%), glaucoma and cornea surgery (4; 12.90%), and trauma from caustication (3; 9.68%).

Patients enucleated for neoplastic diseases or treated with radiotherapy were excluded. Patients with conjunctival fornix insufficient to accommodate the external prosthesis were excluded as well.

In all patients, the CAHY injection procedure was performed at latest 2 years after enucleation or evisceration.

The procedure, alternative treatments, risks, and benefits of the treatment were explained to all patients, and a signed consent form was obtained before injection. One surgeon performed all the diagnostic and surgical procedure.

The severity of enophthalmos was quantified using a Hertel exophthalmometer with the ocular prosthesis in place. The ptosis was graded as follows: 0 absence of ptosis; 1, mild ptosis; 2, moderate degree ptosis; and 3, severe ptosis. Ptosis was assessed by measuring marginal reflex distance 1.

Because the orbital injection of CAHY is painful, it was performed in the operating room with intravenous sedation and retrobulbar injection of anesthesia (2 cc of 1% ropivacain). In the supine position, a total of 1.3 to 2.6 cc of CAHY was injected using a 23-gauge needle. The injection was done transconjunctivally and the surgeon attempted to inject between the medial or lateral rectus and inferior rectus muscles into the intraconal and extraconal space. Furthermore, very deep posterior injections around the orbital apex were avoided to prevent unacceptable spread of the filler into the dangerous zones of the orbital fissures.

Patients included in the study were examined at 3 months and yearly up to at least 10 years after CAHY injection. The results of exophthalmometry, classification of ptosis, and evidence of any complications were recorded. Data were described as frequency and percentage, if categorical, or mean and standard deviation if continuous. Differences between pre and postinjection values were analyzed with Wilcoxon single-rank test. A p-value under 0.05 was considered as significant.

RESULTS

CAHY-injection induced orbital volume augmentation postenucleation or postevisceration for eye trauma were evaluated with a 10-year follow up.

We enrolled 31 patients, 25 males (80.65%) and 6 females (19.35%), with a mean age of 44.0 ± 14.8 years.

The sample characteristics are summarized in the Table.

TABLE.

Sample characteristics

Number of patients included	31
Sex
M	25 (80.65%)
F	6 (19.35%)
Age	44.0 ± 14.8
Indication for surgery
Trauma	20 (64.52%)
Postretinal surgery	4 (12.90%)
Postglaucoma surgery	3 (9.68%)
Postcorneal surgery	1 (3.23%)
Caustic trauma	3 (9.68%)
Typology of surgery
Enucleation	12
Evisceration	19
Preoperative assessment
Hertel exophthalmometry	14.16 ± 2.15 mm
MRD1	2.19 ± 0.79 mm
Injected syringes
1 (1.3 cc)	6 (19.35%)
2 (2.6 cc)	25 (80.65%)
Postoperative assessment
Hertel exophthalmometry
6-month follow up	17.52 ± 1.46 mm
Improvement (mean ± SD; [95% CI])	3.35 ± 0.91 (3.02–3.69) mm
3-year follow up	17.13 ± 1.41 mm
Improvement (mean ± SD; [95% CI])	2.97 ± 1.35 (2.47–3.46) mm
MRD1
6-month follow up	3.48 ± 0.51 mm
3-year follow up	3.71 ± 0.48 mm
Follow up (months)	219 ± 18 (range, 184–240)
Complications
Internal prosthesis extrusion	2 (6.45%)
Ptosis	2 (6.45%)

CI, confidence interval; MRD1, marginal reflex distance 1.

Initial indications for enucleation were trauma (20; 64.52%), sore blind eye from retinal surgery (4; 12.90%), glaucoma and cornea surgery (4; 12.90%), and trauma from caustication (3; 9.68%). All patients had been enucleated at least 2 years previously. The mean amount of preoperative relative enophthalmos measured by Hertel exophthalmometry was 14.16 ± 2.15 mm (range, 11–18 mm).

A mean volume of CAHY of 2.35 ± 0.52 ml (range, 1.3–2.6) was injected.

A mean reduction of 3.35 ± 0.91 mm at 6 months (p < 0.001) and 2.97 ± 1.35 mm at 3 years (p < 0.001) of enophthalmos after treatment was observed. The mean follow-up obtained was 219 ± 18 months (range, 184–240 months). Most patients demonstrated clinical and cosmetic improvement, which was observed to continue for up to 10 years. Two patients had prosthetic extrusion and 2 had ptosis, which was corrected by shortening the palpebral levator muscle.

All patients demonstrated clinical and cosmetic improvement, which was observed to continue for up to 10 years. The presence and persistence of CAHY is demonstrated by MRI images (Figs. 1–3) and by patient images taken with the external prosthesis worn (Figs. 4–6). All the present figures were published after gaining the consent from the patients.

FIG. 1.

A. Axial plane, TSE-T2 weighted image, taken in 2005 shows good diffusion of the filler, which presents a uniformly hyperintense signal; the skin profile is good and symmetrical. B. The same axial, TSE-T2 weighted image taken after 10 years. No significant reabsorption or migration of the filler, nor alteration of the signal intensity.

FIG. 3.

A. Sagittal plane, TSE-T2 weighted image showing good distribution of the filler. B. Sagittal plane, TSE-T2 weighted image taken after 10 years showing no significant resorption, no alteration of the distribution, no hyperintensity of the signal, no fibro-scar tissue due to the filler (no foreign body reaction), no edema nor peri-filler decubitus.

FIG. 4.

A. and B. Patient demonstrated 7 mm of enophthalmos, blepharoptosis, and superior sulcus deformity in the right eye. C. The patient received 2 syringes (2.6 ml) of injectable CAHY with correction of 5-mm enophthalmos. CAHY, calcium hydroxyapatite.

FIG. 6.

The same patient as in Figure 5 observed 10 years after CAHY injection without (A) and with (B) an external prosthesis on. CAHY, calcium hydroxyapatite.

FIG. 2.

A. Coronal plane, TSE-T2 weighted image taken in 2005 showing good filler signal distribution, uniformly hyperintense. B. Coronal TSE-FS-T2 weighted sequence taken after 10 years demonstrating nonresorption of the filler, which keeps a uniformly hyperintense signal.

FIG. 5.

A–C. The same patient of Figure 4 1 week after CAHY injection without external ptosthesis. The same patient with an external prosthesis on (D). CAHY, calcium hydroxyapatite.

Some complications, mostly temporary, were observed in the treatment group. Two patients had limited peribulbar hemorrhage related to the administration of local anesthesia that responded well to pressure patches. No material migration was observed.

Most patients complained of moderate postoperative pain for several days, which could be controlled with oral NSAIDs.

A low complication rate was observed in patients with PESS.

DISCUSSION

The results of this study showed that the relative efficacy of CAHY injection improved the enophthalmos, sulcus deformity, and ptosis. An ideal substance for orbital volume augmentation should have characteristics such as safety, ease of administration, predictable results, and reasonable cost. Also, long lasting filler effects are preferred. As CAHY is a biocompatible material with long-standing effects, it was proposed as a good option for orbital volume augmentation.¹³

CAHY is composed of CaHA (30%) suspended in a gel support (70%) consisting of sodium carboxymethylcellulose, glycerin, and water. CaHA microspheres range from 25 to 45 µm in size and are identical to the inorganic components of bone and teeth. CaHA is a nonirritating bioceramic and is biocompatible.^24–26

When CAHY is injected into tissue, it provides an immediate 1-to-1 level of correction. Over the course of 3 to 6 months, the gel carrier is degraded and the remaining CaHA particles serve as a scaffold for new collagen deposition across a fibroblastic response. This process provides an extensive, semipermanent solution. Interestingly, studies have shown that collagen growth occurs around the microspheres, replacing the gel vehicle, and therefore potentially providing a long-lasting effect.^25,26

This lasting improvement is not attributable to an inflammatory process, as no clinical evidence was observed. Additionally, long-term maintenance of orbital volume with little loss of efficacy has been observed. That is in contrast to the experience with the use of fillers for aesthetic purposes, where a shorter half-life has been observed.^13,27 This phenomenon can be explained through several mechanisms: first, it is possible that the collagen that forms in the orbit is more compacted than in other locations, and the continuous dynamic muscular actions that create facial wrinkles are not present in the orbit. Second, the blood supply to the enucleated orbit is likely to be decreased, leading to reduced monocyte surveillance and thus reduced clearance of CaHA microspheres.^26,28 Furthermore, the orbit is a privileged space with fewer lymphatic vessels than the subcutaneous tissue, which further limits the removal of the filler.

Despite our extensive experience on CAHY in orbital volume augmentation, it has only received FDA approval for facial aesthetic uses such as nasolabial folds and for the correction of HIV-associated lipoatrophy, and its use for orbital volume augmentation is still off-label.^28–30

Our choice of using a CAHY-based filler rather than using other methods is based on several factors such as PESS severity, the specific location of volume loss, the advantage of avoiding fibrotic phenomena, the speed in obtaining the desired result, and the no-hospitalization factor. That is possible as CAHY does not require allergy testing and is ready for immediate use. Furthermore, CAHY injection has been used for many years in a variety of reconstructive surgeries and dentistry, and CAHY has been proven to be biocompatible and immediately effective.^30,31

In our study, enophthalmos and superior sulcus depth were reduced in all patients at all postoperative follow-up visits. Although our patients had a history of trauma and multiple reconstructive orbital surgeries with areas of fibrosis of the orbital structures, the results were maintained throughout the follow-up period. There was no filler migration, a potential complication of intraorbital material injection. The trick for placing the filler posteriorly enough is to inject the filler into the desired location and stop the injection before withdrawing the needle. Injecting fillers at multiple sites in the deep socket area is one method we suggest preventing this complication. Transient adverse effects such as bruising, edema, erythema, pain, and itching are what are called “injection site reactions” and are a consequence of the trauma during the injection. These types of adverse effects are intrinsic to the treatment and therefore should not be classified as true adverse events. Furthermore, these reactions are not specific to the filler and they can occur regardless of the filler used.^32–34

We suggest performing retrobulbar injection of anesthesia (2 cc of 1% ropivacain) and we prefer connecting the female luer lock on a dual check valve to a control syringe. This way we believe the operator can reduce the risk of injection-related complications. In fact, only 1 patient had peribulbar hemorrhage from the administration of anesthesia before performing the procedure. Because of this we postponed the procedure due to the difficulty in judging the volume to be injected. Moreover, it is crucial to inject only a small amount of filler into the intraconal space, as it can limit the final correction. In fact, the resistance produced by the extraocular muscles can prevent anterior mobilization of the prosthetic implant and limit the amount of volume to be added. Furthermore, the intraconal injection induce an oculocardiac reflex by tensing the extraocular muscles.

Recently, injectable fillers have been used for the correction of posttraumatic enophthalmos in blind eyes.^33–35 We have no experience of injecting CAHY in these patients, but we are encouraged by the results we have obtained so far. With minor enophthalmos in sighted eyes, this will likely become a viable option for correction with less risk and morbidity than extensive surgery. Based on these reports, we believe that it would be appropriate to keep the prosthesis in place during the filler injection as the volume augmentation and tissues’ advancement would get easier to assess. This way, the filler would be placed along the posterior orbital floor to move the prosthesis forward and superiorly more accurately.

In our cases, enophthalmos reduction of 3.35 ± 0.91 (3.02–3.69) mm was achieved with an injection of ≈2.1 ml of CAHY and occurred in all primary injections. It is therefore reasonable to say that CAHY-base fillers can be used to increase the orbital volume and thus allow for thinner external prostheses if problems of discomfort in wearing them occur.

Finally, in our study, upper eyelid ptosis increased in 2 cases. Probably the chronic inflammation induced by the intraorbital filler injection led to a malfunction of the levator muscle or aponeurosis dehiscence, and this relatively rare complication must be taken into account.

CONCLUSIONS

Injectable CAHY provides safe, simple, repeatable, and cost-effective technique to treat volume deficiency in the enophthalmic orbit in the long term. The volume augmentation obtained with this semipermanent filler demonstrated a lasting effect in the orbit with negligible loss of volume at 10 years.