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Gadolinium-enhanced Magnetic Resonance Imaging Assessment of Hydroxyapatite Orbital Implants
Gadolinium-enhanced Magnetic Resonance Imaging Assessment of Hydroxyapatite Orbital Implants JOSEPH P. SPIRNAK, MD., NESTOR NI EVES, MD., DONALD A. HOLLSTEN, MD., WILLIAM C. WHITE, MD., AND TODD A. BETZ
• PURPOSE: Successful prosthesis attachment depends on complete vascularization of porous coral line hydroxyapatite when it is used as an orbital implant. We retrospectively assessed the utility of gadolinium-enhanced magnetic resonance imaging to evaluate and characterize the temporal progres sion of this fibrovascular process, which has been histologically documented elsewhere. • METHODS: Serial Τ,-weighted gadoliniumenhanced orbital magnetic resonance examina tions were performed in five patients receiving hydroxyapatite orbital implants. Retrospective evaluation of the enhancement patterns was per formed. Magnetic resonance imaging enhance ment patterns guided timing of final drilling for prosthesis fixation. • RESULTS: Serial gadolinium-enhanced T^ weighted sequences consistently demonstrated centrally advancing, peripheral enhancement cen tered on the drilled access channels. Progression over time varied, with the following two patterns demonstrated: ( 1 ) rapid peripheral enhancement, which led to diffuse enhancement (three patients); Accepted for publication Oct. 11, 1994. From the Department of Radiology, Dwight David Eisenhower Army Medical Center, Fort Gordon, Georgia (Dr. Spirnak); and the Depart ment of Radiology, Brooke Army Medical Center, Fort Sam Houston, Texas (Drs. Nieves, Hollsten, and White and Mr. Betz). These data were presented in part at the International Congress of Radiology, Singapore, June 23-28, 1994. The opinions or assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the Department of the Army or the Depart ment of Defense. Reprint requests to Joseph P. Spirnak, M.D., Department of Radiol ogy, Dwight David Eisenhower Army Medical Center, HSHF-R, Fort Gordon, GA 30905-5650; fax: (706) 791-5386. VOL.119, No. 4
and (2) enhancement limited to the periphery, which failed to advance centrally. • CONCLUSIONS: The temporal enhancement seen on magnetic resonance imaging is identical to the histologically proven fibrovascular ingrowth pattern and most likely reflects this process. Mag netic resonance imaging can identify progression of fibrovascular ingrowth into the hydroxyapatite orbital implants and guide surgical planning. It may also identify implants that fail to vascularize, thereby preventing the morbidity encountered by drilling into an avascular hydroxyapatite implant.
C
ALCIUM PHOSPHATE HYDROXYAPATITE IS DErived from the conversion of the calcium carbonate exoskeleton of several reef-building, marine corals.1'3 It has been used as an alloplastic bone graft substitute for a variety of reconstructive procedures,3 including use as an ocular implant (Biomatrix Ocular Implant, Integrated Orbital Implants, Inc., San Diego, California) since 1985 under the research protocol of Arthur Perry, M.D. (oral com munication, November 1991). It was approved by the Food and Drug Administration for orbital implanta tion in 1989.2 It has gained increasingly wide accept ance among ophthalmologists in recent years because of the improved appearance of the prosthesis, which has increased mobility and more nearly natural move ment, particularly when the prosthesis is affixed to a peg inserted in the hydroxyapatite implant. Placement of the hydroxyapatite implant and inser tion of a peg in the hydroxyapatite for attachment to the prosthesis is a two-step surgical procedure.2 The
© AMERICAN JOURNAL OF OPHTHALMOLOGY 119:431-440
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first step entails enucleation (or evisceration) of the globe, with placement of the hydroxyapatite sphere (which may or may not be wrapped in donor sciera or similar material) into the muscle cone. The second step entails drilling the hydroxyapatite implant with a 2- to 3-mm-diameter channel, with subsequent place ment of a peg that affixes the prosthesis via a ball-and-socket joint. Drilling of the implant is de layed until fibrovascularization of the implant has occurred. Gadolinium-enhanced magnetic resonance ima ging4 and bone scintigraphy5 have been used to assess the degree of fibrovascular ingrowth. There is no definite correlation between the extent of hydroxyap atite enhancement on magnetic resonance imaging and the time interval elapsed after implantation.4 This conclusion, however, has been made by compar ing a single enhancement pattern in different patients at various times after implantation. The study by DePotter and associates4 only characterized the interpatient variability in enhancement appearance. We have not found any published descriptions of the temporal appearance (and variability) of enhance ment occurring within an individual patient over time. The purpose of this study was to assess the usefulness of gadolinium-enhanced magnetic reso nance imaging to evaluate and characterize the
temporal progression of this fibrovascular process in individual patients.
PATIENTS AND METHODS ALL PATIENTS UNDERGOING PRIMARY ENUCLEATION OR
requiring secondary anophthalmic revision because of implant migration were educated about hydroxyap atite implants, including the requirements of a second procedure to drill the motility peg hole and of imaging studies to assess the amount of vascular ingrowth. Between January and October 1992, five individuals agreed to undergo the procedure (Table). This study was approved by the Clinical Investiga tions Department, Brooke Army Medical Center. Patients undergoing primary enucleation had the globe removed in the usual fashion, in which the six extraocular muscles were removed from the globe and tagged with 6-0 polyglactin 910 sutures before transection of the optic nerve and removal of the globe from the surgical field. As the first part of the surgical procedure, in patients with previous enucleation and subsequent implant migration who required socket revision, the old implant was removed, and the fibrous capsule was dissected and removed. The four recti muscles were
TABLE SUMMARY OF PATIENT A N D PROCEDURAL DATA POSTOPERATIVE
PATIENT NO., AGE (ÏRS}.
N O . OF
GENDER,
EYE
DIAGNOSIS
1, 27, F, R.E. Extruding implant
PROCEDURE
Socket
socket 3, 31, F, L.E. Phthisis 4, 15, M r L E . Phthsis
432
IMPLANT
IMPLANT
IMAGING
AREA
ENHANCEMENT
PEG
TYPE
S I Z E (MM)
(MOS)
E N H A N C E D (%)
PATTERN
DRILLED
6
Secondary
20
(8 yrs) 4
Enucleation Enucleation
Secondary
20
(12 yrs)
exchange
5, 33, F, L.E. Anophthalmic Enucleation socket
MUSCLES ATTACHED
revision
2, 18, F, R.E. Anophthalmic Implant
MAGNETIC RESONANCE
4 4
4
Primary Primary
Secondary (27 yrs)
20 20
18
2
58
Progressive
4
81
diffuse
7
Diffuse
2
74
Progressive
5
Diffuse
diffuse Progressive
2
76
15
77
5
44
9
64
13
61
17
66
7
29
12
32
17
38
AMERICAN JOURNAL OF OPHTHALMOLOGY
Yes
Yes No
near-diffuse Non progressive No plateau
Nonprogressive No plateau
APRIL 1995
isolated and freed at the distal end of the surrounding soft tissue attachments and tagged with a polyglactin 910 suture. All four recti muscles were identified in this fashion for all patients. The oblique muscles were not actively sought, but they were found during the dissection in one patient. W h e n accurately identified and isolated, the oblique muscles were also tagged for attachment to the implant. From this point, the surgical procedure was identical in both the primary enucleation group (two patients) and the secondary socket revision group (three patients). A Silastic sphere was used to size the orbit for appropriate implant size. The hydroxyapatite sphere was wrapped in eye bank-processed donor sciera (first soaked in saline and then in gentamicin while on the surgical field). The sciera (with existing corneal defect created at time of harvest) was usually too small to surround the hydroxyapatite sphere completely,
and a segment of the implant was left exposed. This defect was positioned posteriorly. Four windows (5 X 10 mm) were cut in the sciera, which corresponded to future sites of attachment of the four recti muscles. The implant was then modified by drilling five radial holes (access channels) directed toward the center of the implant with a l-mm-diameter drill bit. The holes were drilled from the four rectus muscle windows and from the posterior opening (Fig. 1). The implant was then inserted into the socket as deeply as possible. If oblique muscles were to be attached, they were then sutured to the sciera before placing the implant deep into the socket. The four recti muscles were sutured to the anterior edge of the appropriate scierai window, leaving the belly of the muscle exposed to bare hydroxyapatite. The surgical procedure was completed by approximation first of Tenon's capsule followed by conjunctiva. The con-
/
Ur/^fl Fig. 1 (Spirnak and associates). Left, Axial projection depicting the drilling of the access channels into the hydroxyapatite implant. Note how the channels converge on a single focus located centrally, which may account for a central intensely enhancing focus (see Figure 2, bottom right). Right, Coronal projection depicting the drilling of the access channels into the hydroxyapatite implant. Note how the channels converge on a single focus located centrally (see Figure 3, bottom left). VOL.119,
No. 4
MAGNETIC RESONANCE IMAGING OF HYDROXYAPATITE IMPLANTS
433
junctival socket was coated with antibiotic and corticosteroid ointment, and a conformer was placed in the socket behind the eyelids. Magnetic resonance imaging was performed with a 1.5-T superconducting magnet, a general all-purpose head coil, and version 4.8 software. Imaging sequenc es consisted first of a ^-weighted sagittal locator using a multiple-echo, multiplanar pulse sequence with a 5-mm slice thickness, a 2-mm gap, and a field of view of 24 cm. This was followed by axial Tt-weighted images utilizing a pulse repetition time of 500 msec, echo time of 23 msec (500/23), and a matrix of 256 X 192 with four numbers of excitation. A contrast-enhanced axial sequence (intravenous gadopentetate dimeglumine [0.1 mmol/kg of body weight]) ensued with use of fat suppression. Satura tion pulses and no phase wrap were used. From each T,-weighted, enhanced axial examina tion, the image depicting the center (equator) of the implant was identified. This was the slice that most closely approximated the diameter of the implant used (20 mm in most cases). To aid in analysis of the enhancement pattern, the structures medial to each lateral orbital wall were magnified. A total implant area was calculated by outlining the circle of the hydroxyapatite sphere. The peripheral regions of en hancement were outlined by manual tracing that delineated the total enhancement area. The area of enhancement was divided by the total area of the circle, resulting in a percentage area of enhancement (Fig. 2). This percentage area of enhancement was determined at the equator of each implant in each examination. We believe that this is not a statistically established method for estimating regional enhance ment; however, the patterns observed before diffuse enhancement suggest well-delineated regions. This analysis is strictly an attempt to provide some quantifi able (albeit a limited and nonstatistical) method of enhancement interpretation.
RESULTS THE DEMOGRAPHIC, SURGICAL, AND MAGNETIC RESO-
nance imaging enhancement details of the patients, as well as their respective corresponding figures and tables, are given (Table). All five patients had serial
434
examinations. Figures 2 and 3 depict the temporal enhancement patterns seen in two patients (Patients 1 and 5), which are representative of the two patterns of serial enhancement. Figure 4 shows approximate, nonstatistical estimations of the areas of enhance ment described in the Patients and Methods section. Serial examination disclosed an enhancement pat tern that consistently began at the periphery and centered around the access channels. Temporal en hancement demonstrated one of two patterns. One pattern was a consistently progressive enhancement resulting in a diffuse, complete pattern (Fig. 2). The other was a pattern that attained a plateau and failed to demonstrate notable progression (Fig. 3). Tremen dous variability among individuals existed, with some patients attaining diffuse enhancement by five months postoperatively (Patient 2), whereas in other patients diffuse enhancement was missing as late as 17 months postoperatively (Patient 4). All of the implants that had been prospectively identified as having diffuse enhancement (or an estimation approaching 75% area enhancement), were subsequently found to bleed during drilling of the central channel for peg placement. This bleeding confirmed the presence of central fibrovascular in growth. Furthermore, to date these patients have tolerated the implant and peg satisfactorily without infection or other complication.
DISCUSSION ORBITAL IMPLANTS HAVE BEEN MODIFIED FREQUENTLY
since they were first introduced for sockets of eviscer ated (1885)6 and enucleated (1887)7 eyes. Likewise, numerous modifications have been made in the attempt to improve motility and cosmesis of the overlying prosthesis.8 Integrated implants were de signed to improve prosthesis motility by coupling the surfaces of the prosthesis and implant. They can be of two varieties, buried or nonburied. Nonburied, inte grated implants are directly coupled to the prosthesis without intervening conjunctiva. This direct coup ling results in optimum transfer of motility. Migra tion, extrusion, and infection limited the success of this combination.9 Buried, integrated implants, in contrast, have complete growth of conjunctiva ante-
AMERICAN JOURNAL OF OPHTHALMOLOGY
APRIL 1995
Fig. 2 (Spirnak and associates). Patient 1. Top left, Nonenhanced axial ^-weighted image (500/23) demonstrates the intermediate to low intensity of the hydroxyapatite implant in the right eye at two months after implantation. Top right, Gadolinium-enhanced, fat-suppressed ^-weighted axial images two months after implantation. Note the peripheral regional enhancement that corresponds to the surgically created access channels (see Fig. 4, top left). Bottom left, Gadolinium-enhanced, fat-suppressed Tj-weighted axial image at four months after implantation. Outline of the implant and region of enhancement demonstrates the method of manual tracing and determination of the percent area of enhancement (see Fig. 4, top left). Bottom right, Gadolinium-enhanced, fat-suppressed ^-weighted axial image at seven months after implantation (see Fig. 4, top left). Note how the low-intensity (nonenhancing) regions (arrowhead) manifest enhancement on the previous two examinations. This may reflect dense, fibrous changes within the matrix of the porous hydroxyapatite. The central focus of intense enhancement is most likely the convergence point of the access channels (see Figure 1, right).
VOL.
119, No. 4
MAGNETIC RESONANCE IMAGING OF HYDROXYAPATITE IMPLANTS
435
Fig. 3 (Spirnak and associates). Patient 5. Top left, Gadolinium-enhanced, fat-suppressed ^-weighted axial image at seven months after implantation in the left eye. Note the minimal uptake seen at the medial and lateral access channels. Greater uptake was seen along the superior and inferior access channels on a subsequent examination obtained at 12 months after implantation (see Figure 3, bottom left) (see Figure 4, bottom left). Top right, Coronal nonenhanced Τ,-weighted image obtained at 12 months after implantation. Rounded signal voids (curved arrows) represent glass beads surgically placed to expand the orbital volume. Bottom left, Coronal gadolinium-enhanced Tj-weighted image also obtained 12 months after implantation. Note the peripheral enhancement aligned along the linear enhancing drilled access channels (arrowheads) with the greatest enhancement seen along the superior and inferior rather than the medial and lateral access channels. Rounded signal voids (curved arrows) represent glass beads surgically placed to expand the orbital volume (compare this enhancement pattern with Figure 1, right). Bottom right, Gadolinium-enhanced ^-weighted axial image at 17 months after implantation (see Figure 4, bottom left). Note the lack of enhancement progression over time compared with previous patients.
436
AMERICAN JOURNAL OF OPHTHALMOLOGY
APRIL 1995
100
80
94%
/47ο
60
40
20
Time After Implant [mos]
Time After Implant (mos) 100
76%
ÜÜ
In
77%
1
□) 80
^^VJajS^l
W
■ ■
j
■■
^
:
. ; ; ; ; - ; :
:
; - '
E-,:,.v
15 Time After Implant (mos)
38%
Time After Implant (mos)
40%
Fig. 4 (Spirnak and associates). Temporal progression of enhancement in five patients after hydroxyapatite orbital implantation. Top left, Patient 1 (see Figure 2). Top right, Patient 2. Middle left, Patient 3. Middle right, Patient 4. Bottom left, Patient 5 (see Figure 3).
Time After Implant (mos)
VOL.119, No. 4
MAGNETIC RESONANCE IMAGING OF HYDROXYAPATITE IMPLANTS
437
rior to the surface of the implant. Coupling is made through this intervening conjunctiva, which provides an additional protective barrier from infection that is not present in the nonburied, integrated implants. In the patients attaining complete enhancement in this series and after drilling of the central access channel for peg placement, conjunctiva was allowed to invade the channel before peg placement, thus maintaining the buried status of the hydroxyapatite implant. The peg was then placed within this conjunctiva-lined channel. The biocompatibility and nonallergenic properties of hydroxyapatite are ideally suited to function as a buried, integrated implant.10 The replamineform process11 converts the calcium carbonate exoskeleton of marine, reef-building corals into calcium phosphate hydroxyapatite.1'3 The regular system of interconnecting pores (50 to 500 μιτι) remarkably is unaltered through this process, resulting in a latticework that resembles the haversian system of normal cancellous bone.2 Structurally, this porous architecture provides a suitable scaffold for rapid ingrowth of vascularized connective tissue. Such ingrowth has been verified histologically in orbital implants as early as four weeks after implantation.12 These properties enable it to be used in various musculoskeletal and maxillofacial procedures.3 Hy droxyapatite has been associated only with a mild chronic inflammation under conditions of experi mental bacterial infection.13 The absence of blind passages or cul-de-sacs most likely accounts for the high resistance to infection and minimal foreign body inflammation.14 Several details of the surgical procedure and im plant manipulation are important to understand the imaging characteristics of the hydroxyapatite implant. Creating a scierai window15 and drilling centrally converging access channels at the site of rectus muscle attachment2,5 are presumed to expedite fibrovascular ingrowth by increasing the area of exposure. Both of these modifications were used in these patients. Various imaging modalities have been used to evaluate the vascular status of hydroxyapatite im plants. In one histologically confirmed case,12 only contrast-enhanced computed tomography was per formed. Imaging of the implant was relatively unre markable, showing a bone density sphere that did not
438
enhance appreciably with contrast administration.12 Color Doppler imaging is able to detect vascularity at the extraocular muscle-scleral window insertion; however, vascular ingrowth into the calcific hydroxy apatite is obscured because of sound attenuation.4 Nuclear scintigraphy and most recently magnetic resonance imaging are the two current primary mo dalities. Hydroxyapatite implants manifest isointensity and hypointensity on T^ and T2-weighted sequences, respectively. The enhancement pattern has been studied after intravenous gadolinium injection, albeit without histologie verification.4,9 With this series we conclude that ^-weighted sequences (with or with out fat suppression) after intravenous gadolinium injection provide the most contributory information pertaining to the implant's vascular status. If cost containment is a factor, an abbreviated magnetic resonance examination may be limited to a sagittal (Tj-weighted) locator followed by two or three contig uous, axial Tj-weighted images (with or without fat suppression) through the equator of the implant after gadolinium injection. All patients in this series demonstrated peripheral enhancement patterns, which over time progressed (with variability) toward the center of the implant. This peripheral pattern was somewhat asymmetric, with an advancing edge radiating from the scierai windows and their accompanying access channels. This enhancement pattern is identical to the two previously reported12'16 histologie patterns of fibrovascular ingrowth. Progression of enhancement in this series was variable, which may be caused by differences in angiogenesis among patients. Of interest, the secon dary implants in this series showed an aggressive pattern of enhancement with successful drilling by as early as five months (Patient 2). The two primary implants (Patients 3 and 4), however, did not achieve a complete, diffuse pattern 15 and 17 months, respec tively, after implantation. Only one of the secondary implants (Patient 5) showed little enhancement pro gression after 25 months of follow-up. Although motility may be more limited clinically with secon dary implants (because of somefibrosisor atrophy of the extraocular muscles), our results indicate that the potential for vascularization certainly exists and is
AMERICAN JOURNAL OF OPHTHALMOLOGY
APRIL 1995
perhaps greater when compared with primary implan tation. Study of a larger series of patients is necessary to verify this, however. The somewhat well-demarcated, intense enhance ment encountered early after implantation repeatedly demonstrated less definition and intensity over time (Fig. 2, bottom right). An understanding of the cellular changes occurring within the interstices of hydroxyapatite may explain this finding. The biologic behavior of the surrounding bone with regard to the hydroxyapatite implanted into the maxillofacial skeleton10 and as a bone graft substi tute17 may account for the long-term imaging findings encountered in this series. Compared with the imme diate postoperative period, no marked change in either radiodensity or discreteness of the margins was seen in hydroxyapatite orthopedic implants up to 24 months postoperatively. When osseous union oc curred, a complex network of multidirectional osseous projections was seen extending into the implant pores from the adjacent osteoid tissue.10 No osteoclast or other evidence of bone résorption or remodeling was seen. Abundant vascular ingrowth was identified central to the peripheral osseous ingrowth. Interest ingly, implants that healed with a fibrous (nonosseous) union lacked bone ingrowth, which indicates that direct continuity of adjacent viable bone is a prerequisite for this process of bone ingrowth.10 Hydroxyapatite, when used as an orbital implant, may evoke a different host-tissue response. In contrast to having a direct interface with adjacent viable trabecular bone and periosteum, it is placed into a scierai shell (that undergoes résorption),12 which is subsequently embedded into the soft tissues of the orbit, without exposure to any stress or compressive forces. A similar animal model involved placement of hydroxyapatite particles into buccal soft tissues.18 Hydroxyapatite (with a rounded shape) was predomi nantly coated with mature collagen with minimal foreign-body giant-cell reaction. Histologie studies of hydroxyapatite used as an orbital implant are scarce.12,16 Fibrous tissue found at the periphery of hydroxyapatite orbital implants has been reported as dense and arranged in a lamellar pattern compared with loosefibrovasculartissue with edematous matrix seen at the advancing edge more centrally.16 These cellular changes (namely, centrally directed fibrovas
VOL.119, N o . 4
cular ingrowth with peripheral replacement by dense collagen or connective tissue) most likely account for the reduced enhancement seen with time. The purpose of imaging the hydroxyapatite im plant is to determine complete vascularity and to avoid drilling the final channel for peg placement into an avascular implant. The goal is to prevent prema ture drilling and avoid associated morbidity (and cost) of infection and implant failure. Our interpreta tion of the enhancement pattern in this series has altered surgical treatment, as final drilling for peg placement is delayed until there is a diffuse (or near diffuse) enhancement pattern. We have also demon strated an improvement in the surgical outcome when the enhancement interpretation guides surgical plan ning. Although this series was small, no cases of infection have been encountered after final drilling for peg placement. In conclusion, we have shown that the hydroxyapa tite enhancement pattern after implantation consist ently has a peripheral origin centered over the access channels and centripetal progression. This pattern is identical to histologie fibrovascular ingrowth and most likely reflects this process. In most patients, this enhancement pattern consistently showed progres sion, albeit variable. However, failure of progression has also been observed. Because of this amount of variability, we must question the efficacy of final drilling and peg placement at an arbitrarily scheduled time after implantation. Timing the peg insertion according to fibrovascular progression may prevent morbidity incurred by drilling into an implant that is not completely vascularized. In this era of cost containment, several important questions need to be asked. Is postimplant magnetic resonance imaging examination justified? Is the cost of magnetic resonance imaging less than the cost incurred by an implant aborted because of drilling that was too premature? Can imaging prevent the morbidity of postimplant infection? Certainly some patients in this series have failed to attain a diffuse enhancement pattern. Would drilling into an implant with this pattern result in an avascular channel and thus predispose to infection? Perhaps the most impor tant information that magnetic resonance imaging can provide is to identify the patients who fail to vascularize their hydroxyapatite implant completely.
MAGNETIC RESONANCE IMAGING OF HYDROXYAPATITE IMPLANTS
439
Such patients may require additional surgical inter vention to encourage this process before final drilling and peg placement.
REFERENCES 1. Roy DM, Linnehan SK. Hydroxyapatite formed from coral skeletal carbonate by hydrothermal exchange. Nature 1974;247:220-2. 2. Dutton JJ. Corallin hydroxyapatite as an ocular implant. Ophthalmology 1991;98:370-7. 3. Sartoris DJ, Gershuni DH, Akeson WH, Holmes RE, Resnick D. Corallin hydroxyapatite bone graft substitutes: preliminary report of radiographie evaluation. Radiology 1986;159:133-7. 4. DePotter P, Shields CL, Shields JA, Flanders AE, Rao VM. Role of magnetic resonance imaging in the evaluation of the hydroxyapatite orbital implant. Ophthalmology 1992; 99:824-30. 5. Ferrone PJ, Dutton JJ. Rate of vascularization of coralline hydroxyapatite ocular implants. Ophthalmology 1992; 99:376-9. 6. Mules PH. Evisceration of the globe, with artificial vitreous. Trans Ophthalmol Soc U K 1885;5:200-6. 7. Frost WA. What is the best method of dealing with a lost eye? BrMedJ 1887;1:1153-4. 8. Soll DB. The anophthalmic socket. Ophthalmology 1982;89:407-23.
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9. Shields CL, Shields JA, De Potter P. Hydroxyapatite orbital implant after enucleation: experience with initial 100 con secutive cases. Arch Ophthalmol 1992;110:333-8. 10. Rosen HM, McFarland MM. The biologic behavior of hydroxyapatite implanted into the maxillofacial skeleton. Plast Reconstr Surg 1990;85:718-23. 11. White EW, Weber JN, Roy DM, Owen EL, Chiroff RT, White RA. Replamineform porous biomaterials for hard tissue implant applications. J Biomed Mater Res 1975;6:23-7. 12. Shields CL, Shields JA, Eagle RC Jr, De Potter P. Histopathologic evidence of fibrovascular ingrowth four weeks after placement of the hydroxyapatite orbital implant. Am J Ophthalmol 1991;111:363-6. 13. Reznick JB, Gilmore W O Host response to infection of a subperiosteal hydroxylapatite implant. Oral Surg Oral Med Oral Pathol 1989;67:665-72. 14. Holmes RE. Bone regeneration within a coralline hydroxyap atite implant. Plast Reconstr Surg 1979;63:626-33. 15. Perry AC. Advances in enucleation. Ophthalmic Clin North Am 1991;4:173-82. 16. Rosner M, Edward DP, Tso MOM. Foreign-body giant-cell reaction to the hydroxyapatite orbital implant [letter]. Arch Ophthalmol 1992;110:173-4. 17. Holmes RE, Hagler HK. Porous hydroxylapatite as a bone graft substitute in mandibular contour augmentation: a histometric study. J Oral Maxillofac Surg 1987;45:421-9. 18. Misiek DJ, Kent JN, Carr RF. Soft tissue responses to hydroxyapatite particles of different shapes. J Oral Maxillofac Surg 1984;42:150-60.
AMERICAN JOURNAL OF OPHTHALMOLOGY
APRIL
1995
• PURPOSE: Successful prosthesis attachment depends on complete vascularization of porous coral line hydroxyapatite when it is used as an orbital implant. We retrospectively assessed the utility of gadolinium-enhanced magnetic resonance imaging to evaluate and characterize the temporal progres sion of this fibrovascular process, which has been histologically documented elsewhere. • METHODS: Serial Τ,-weighted gadoliniumenhanced orbital magnetic resonance examina tions were performed in five patients receiving hydroxyapatite orbital implants. Retrospective evaluation of the enhancement patterns was per formed. Magnetic resonance imaging enhance ment patterns guided timing of final drilling for prosthesis fixation. • RESULTS: Serial gadolinium-enhanced T^ weighted sequences consistently demonstrated centrally advancing, peripheral enhancement cen tered on the drilled access channels. Progression over time varied, with the following two patterns demonstrated: ( 1 ) rapid peripheral enhancement, which led to diffuse enhancement (three patients); Accepted for publication Oct. 11, 1994. From the Department of Radiology, Dwight David Eisenhower Army Medical Center, Fort Gordon, Georgia (Dr. Spirnak); and the Depart ment of Radiology, Brooke Army Medical Center, Fort Sam Houston, Texas (Drs. Nieves, Hollsten, and White and Mr. Betz). These data were presented in part at the International Congress of Radiology, Singapore, June 23-28, 1994. The opinions or assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the Department of the Army or the Depart ment of Defense. Reprint requests to Joseph P. Spirnak, M.D., Department of Radiol ogy, Dwight David Eisenhower Army Medical Center, HSHF-R, Fort Gordon, GA 30905-5650; fax: (706) 791-5386. VOL.119, No. 4
and (2) enhancement limited to the periphery, which failed to advance centrally. • CONCLUSIONS: The temporal enhancement seen on magnetic resonance imaging is identical to the histologically proven fibrovascular ingrowth pattern and most likely reflects this process. Mag netic resonance imaging can identify progression of fibrovascular ingrowth into the hydroxyapatite orbital implants and guide surgical planning. It may also identify implants that fail to vascularize, thereby preventing the morbidity encountered by drilling into an avascular hydroxyapatite implant.
C
ALCIUM PHOSPHATE HYDROXYAPATITE IS DErived from the conversion of the calcium carbonate exoskeleton of several reef-building, marine corals.1'3 It has been used as an alloplastic bone graft substitute for a variety of reconstructive procedures,3 including use as an ocular implant (Biomatrix Ocular Implant, Integrated Orbital Implants, Inc., San Diego, California) since 1985 under the research protocol of Arthur Perry, M.D. (oral com munication, November 1991). It was approved by the Food and Drug Administration for orbital implanta tion in 1989.2 It has gained increasingly wide accept ance among ophthalmologists in recent years because of the improved appearance of the prosthesis, which has increased mobility and more nearly natural move ment, particularly when the prosthesis is affixed to a peg inserted in the hydroxyapatite implant. Placement of the hydroxyapatite implant and inser tion of a peg in the hydroxyapatite for attachment to the prosthesis is a two-step surgical procedure.2 The
© AMERICAN JOURNAL OF OPHTHALMOLOGY 119:431-440
431
first step entails enucleation (or evisceration) of the globe, with placement of the hydroxyapatite sphere (which may or may not be wrapped in donor sciera or similar material) into the muscle cone. The second step entails drilling the hydroxyapatite implant with a 2- to 3-mm-diameter channel, with subsequent place ment of a peg that affixes the prosthesis via a ball-and-socket joint. Drilling of the implant is de layed until fibrovascularization of the implant has occurred. Gadolinium-enhanced magnetic resonance ima ging4 and bone scintigraphy5 have been used to assess the degree of fibrovascular ingrowth. There is no definite correlation between the extent of hydroxyap atite enhancement on magnetic resonance imaging and the time interval elapsed after implantation.4 This conclusion, however, has been made by compar ing a single enhancement pattern in different patients at various times after implantation. The study by DePotter and associates4 only characterized the interpatient variability in enhancement appearance. We have not found any published descriptions of the temporal appearance (and variability) of enhance ment occurring within an individual patient over time. The purpose of this study was to assess the usefulness of gadolinium-enhanced magnetic reso nance imaging to evaluate and characterize the
temporal progression of this fibrovascular process in individual patients.
PATIENTS AND METHODS ALL PATIENTS UNDERGOING PRIMARY ENUCLEATION OR
requiring secondary anophthalmic revision because of implant migration were educated about hydroxyap atite implants, including the requirements of a second procedure to drill the motility peg hole and of imaging studies to assess the amount of vascular ingrowth. Between January and October 1992, five individuals agreed to undergo the procedure (Table). This study was approved by the Clinical Investiga tions Department, Brooke Army Medical Center. Patients undergoing primary enucleation had the globe removed in the usual fashion, in which the six extraocular muscles were removed from the globe and tagged with 6-0 polyglactin 910 sutures before transection of the optic nerve and removal of the globe from the surgical field. As the first part of the surgical procedure, in patients with previous enucleation and subsequent implant migration who required socket revision, the old implant was removed, and the fibrous capsule was dissected and removed. The four recti muscles were
TABLE SUMMARY OF PATIENT A N D PROCEDURAL DATA POSTOPERATIVE
PATIENT NO., AGE (ÏRS}.
N O . OF
GENDER,
EYE
DIAGNOSIS
1, 27, F, R.E. Extruding implant
PROCEDURE
Socket
socket 3, 31, F, L.E. Phthisis 4, 15, M r L E . Phthsis
432
IMPLANT
IMPLANT
IMAGING
AREA
ENHANCEMENT
PEG
TYPE
S I Z E (MM)
(MOS)
E N H A N C E D (%)
PATTERN
DRILLED
6
Secondary
20
(8 yrs) 4
Enucleation Enucleation
Secondary
20
(12 yrs)
exchange
5, 33, F, L.E. Anophthalmic Enucleation socket
MUSCLES ATTACHED
revision
2, 18, F, R.E. Anophthalmic Implant
MAGNETIC RESONANCE
4 4
4
Primary Primary
Secondary (27 yrs)
20 20
18
2
58
Progressive
4
81
diffuse
7
Diffuse
2
74
Progressive
5
Diffuse
diffuse Progressive
2
76
15
77
5
44
9
64
13
61
17
66
7
29
12
32
17
38
AMERICAN JOURNAL OF OPHTHALMOLOGY
Yes
Yes No
near-diffuse Non progressive No plateau
Nonprogressive No plateau
APRIL 1995
isolated and freed at the distal end of the surrounding soft tissue attachments and tagged with a polyglactin 910 suture. All four recti muscles were identified in this fashion for all patients. The oblique muscles were not actively sought, but they were found during the dissection in one patient. W h e n accurately identified and isolated, the oblique muscles were also tagged for attachment to the implant. From this point, the surgical procedure was identical in both the primary enucleation group (two patients) and the secondary socket revision group (three patients). A Silastic sphere was used to size the orbit for appropriate implant size. The hydroxyapatite sphere was wrapped in eye bank-processed donor sciera (first soaked in saline and then in gentamicin while on the surgical field). The sciera (with existing corneal defect created at time of harvest) was usually too small to surround the hydroxyapatite sphere completely,
and a segment of the implant was left exposed. This defect was positioned posteriorly. Four windows (5 X 10 mm) were cut in the sciera, which corresponded to future sites of attachment of the four recti muscles. The implant was then modified by drilling five radial holes (access channels) directed toward the center of the implant with a l-mm-diameter drill bit. The holes were drilled from the four rectus muscle windows and from the posterior opening (Fig. 1). The implant was then inserted into the socket as deeply as possible. If oblique muscles were to be attached, they were then sutured to the sciera before placing the implant deep into the socket. The four recti muscles were sutured to the anterior edge of the appropriate scierai window, leaving the belly of the muscle exposed to bare hydroxyapatite. The surgical procedure was completed by approximation first of Tenon's capsule followed by conjunctiva. The con-
/
Ur/^fl Fig. 1 (Spirnak and associates). Left, Axial projection depicting the drilling of the access channels into the hydroxyapatite implant. Note how the channels converge on a single focus located centrally, which may account for a central intensely enhancing focus (see Figure 2, bottom right). Right, Coronal projection depicting the drilling of the access channels into the hydroxyapatite implant. Note how the channels converge on a single focus located centrally (see Figure 3, bottom left). VOL.119,
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junctival socket was coated with antibiotic and corticosteroid ointment, and a conformer was placed in the socket behind the eyelids. Magnetic resonance imaging was performed with a 1.5-T superconducting magnet, a general all-purpose head coil, and version 4.8 software. Imaging sequenc es consisted first of a ^-weighted sagittal locator using a multiple-echo, multiplanar pulse sequence with a 5-mm slice thickness, a 2-mm gap, and a field of view of 24 cm. This was followed by axial Tt-weighted images utilizing a pulse repetition time of 500 msec, echo time of 23 msec (500/23), and a matrix of 256 X 192 with four numbers of excitation. A contrast-enhanced axial sequence (intravenous gadopentetate dimeglumine [0.1 mmol/kg of body weight]) ensued with use of fat suppression. Satura tion pulses and no phase wrap were used. From each T,-weighted, enhanced axial examina tion, the image depicting the center (equator) of the implant was identified. This was the slice that most closely approximated the diameter of the implant used (20 mm in most cases). To aid in analysis of the enhancement pattern, the structures medial to each lateral orbital wall were magnified. A total implant area was calculated by outlining the circle of the hydroxyapatite sphere. The peripheral regions of en hancement were outlined by manual tracing that delineated the total enhancement area. The area of enhancement was divided by the total area of the circle, resulting in a percentage area of enhancement (Fig. 2). This percentage area of enhancement was determined at the equator of each implant in each examination. We believe that this is not a statistically established method for estimating regional enhance ment; however, the patterns observed before diffuse enhancement suggest well-delineated regions. This analysis is strictly an attempt to provide some quantifi able (albeit a limited and nonstatistical) method of enhancement interpretation.
RESULTS THE DEMOGRAPHIC, SURGICAL, AND MAGNETIC RESO-
nance imaging enhancement details of the patients, as well as their respective corresponding figures and tables, are given (Table). All five patients had serial
434
examinations. Figures 2 and 3 depict the temporal enhancement patterns seen in two patients (Patients 1 and 5), which are representative of the two patterns of serial enhancement. Figure 4 shows approximate, nonstatistical estimations of the areas of enhance ment described in the Patients and Methods section. Serial examination disclosed an enhancement pat tern that consistently began at the periphery and centered around the access channels. Temporal en hancement demonstrated one of two patterns. One pattern was a consistently progressive enhancement resulting in a diffuse, complete pattern (Fig. 2). The other was a pattern that attained a plateau and failed to demonstrate notable progression (Fig. 3). Tremen dous variability among individuals existed, with some patients attaining diffuse enhancement by five months postoperatively (Patient 2), whereas in other patients diffuse enhancement was missing as late as 17 months postoperatively (Patient 4). All of the implants that had been prospectively identified as having diffuse enhancement (or an estimation approaching 75% area enhancement), were subsequently found to bleed during drilling of the central channel for peg placement. This bleeding confirmed the presence of central fibrovascular in growth. Furthermore, to date these patients have tolerated the implant and peg satisfactorily without infection or other complication.
DISCUSSION ORBITAL IMPLANTS HAVE BEEN MODIFIED FREQUENTLY
since they were first introduced for sockets of eviscer ated (1885)6 and enucleated (1887)7 eyes. Likewise, numerous modifications have been made in the attempt to improve motility and cosmesis of the overlying prosthesis.8 Integrated implants were de signed to improve prosthesis motility by coupling the surfaces of the prosthesis and implant. They can be of two varieties, buried or nonburied. Nonburied, inte grated implants are directly coupled to the prosthesis without intervening conjunctiva. This direct coup ling results in optimum transfer of motility. Migra tion, extrusion, and infection limited the success of this combination.9 Buried, integrated implants, in contrast, have complete growth of conjunctiva ante-
AMERICAN JOURNAL OF OPHTHALMOLOGY
APRIL 1995
Fig. 2 (Spirnak and associates). Patient 1. Top left, Nonenhanced axial ^-weighted image (500/23) demonstrates the intermediate to low intensity of the hydroxyapatite implant in the right eye at two months after implantation. Top right, Gadolinium-enhanced, fat-suppressed ^-weighted axial images two months after implantation. Note the peripheral regional enhancement that corresponds to the surgically created access channels (see Fig. 4, top left). Bottom left, Gadolinium-enhanced, fat-suppressed Tj-weighted axial image at four months after implantation. Outline of the implant and region of enhancement demonstrates the method of manual tracing and determination of the percent area of enhancement (see Fig. 4, top left). Bottom right, Gadolinium-enhanced, fat-suppressed ^-weighted axial image at seven months after implantation (see Fig. 4, top left). Note how the low-intensity (nonenhancing) regions (arrowhead) manifest enhancement on the previous two examinations. This may reflect dense, fibrous changes within the matrix of the porous hydroxyapatite. The central focus of intense enhancement is most likely the convergence point of the access channels (see Figure 1, right).
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Fig. 3 (Spirnak and associates). Patient 5. Top left, Gadolinium-enhanced, fat-suppressed ^-weighted axial image at seven months after implantation in the left eye. Note the minimal uptake seen at the medial and lateral access channels. Greater uptake was seen along the superior and inferior access channels on a subsequent examination obtained at 12 months after implantation (see Figure 3, bottom left) (see Figure 4, bottom left). Top right, Coronal nonenhanced Τ,-weighted image obtained at 12 months after implantation. Rounded signal voids (curved arrows) represent glass beads surgically placed to expand the orbital volume. Bottom left, Coronal gadolinium-enhanced Tj-weighted image also obtained 12 months after implantation. Note the peripheral enhancement aligned along the linear enhancing drilled access channels (arrowheads) with the greatest enhancement seen along the superior and inferior rather than the medial and lateral access channels. Rounded signal voids (curved arrows) represent glass beads surgically placed to expand the orbital volume (compare this enhancement pattern with Figure 1, right). Bottom right, Gadolinium-enhanced ^-weighted axial image at 17 months after implantation (see Figure 4, bottom left). Note the lack of enhancement progression over time compared with previous patients.
436
AMERICAN JOURNAL OF OPHTHALMOLOGY
APRIL 1995
100
80
94%
/47ο
60
40
20
Time After Implant [mos]
Time After Implant (mos) 100
76%
ÜÜ
In
77%
1
□) 80
^^VJajS^l
W
■ ■
j
■■
^
:
. ; ; ; ; - ; :
:
; - '
E-,:,.v
15 Time After Implant (mos)
38%
Time After Implant (mos)
40%
Fig. 4 (Spirnak and associates). Temporal progression of enhancement in five patients after hydroxyapatite orbital implantation. Top left, Patient 1 (see Figure 2). Top right, Patient 2. Middle left, Patient 3. Middle right, Patient 4. Bottom left, Patient 5 (see Figure 3).
Time After Implant (mos)
VOL.119, No. 4
MAGNETIC RESONANCE IMAGING OF HYDROXYAPATITE IMPLANTS
437
rior to the surface of the implant. Coupling is made through this intervening conjunctiva, which provides an additional protective barrier from infection that is not present in the nonburied, integrated implants. In the patients attaining complete enhancement in this series and after drilling of the central access channel for peg placement, conjunctiva was allowed to invade the channel before peg placement, thus maintaining the buried status of the hydroxyapatite implant. The peg was then placed within this conjunctiva-lined channel. The biocompatibility and nonallergenic properties of hydroxyapatite are ideally suited to function as a buried, integrated implant.10 The replamineform process11 converts the calcium carbonate exoskeleton of marine, reef-building corals into calcium phosphate hydroxyapatite.1'3 The regular system of interconnecting pores (50 to 500 μιτι) remarkably is unaltered through this process, resulting in a latticework that resembles the haversian system of normal cancellous bone.2 Structurally, this porous architecture provides a suitable scaffold for rapid ingrowth of vascularized connective tissue. Such ingrowth has been verified histologically in orbital implants as early as four weeks after implantation.12 These properties enable it to be used in various musculoskeletal and maxillofacial procedures.3 Hy droxyapatite has been associated only with a mild chronic inflammation under conditions of experi mental bacterial infection.13 The absence of blind passages or cul-de-sacs most likely accounts for the high resistance to infection and minimal foreign body inflammation.14 Several details of the surgical procedure and im plant manipulation are important to understand the imaging characteristics of the hydroxyapatite implant. Creating a scierai window15 and drilling centrally converging access channels at the site of rectus muscle attachment2,5 are presumed to expedite fibrovascular ingrowth by increasing the area of exposure. Both of these modifications were used in these patients. Various imaging modalities have been used to evaluate the vascular status of hydroxyapatite im plants. In one histologically confirmed case,12 only contrast-enhanced computed tomography was per formed. Imaging of the implant was relatively unre markable, showing a bone density sphere that did not
438
enhance appreciably with contrast administration.12 Color Doppler imaging is able to detect vascularity at the extraocular muscle-scleral window insertion; however, vascular ingrowth into the calcific hydroxy apatite is obscured because of sound attenuation.4 Nuclear scintigraphy and most recently magnetic resonance imaging are the two current primary mo dalities. Hydroxyapatite implants manifest isointensity and hypointensity on T^ and T2-weighted sequences, respectively. The enhancement pattern has been studied after intravenous gadolinium injection, albeit without histologie verification.4,9 With this series we conclude that ^-weighted sequences (with or with out fat suppression) after intravenous gadolinium injection provide the most contributory information pertaining to the implant's vascular status. If cost containment is a factor, an abbreviated magnetic resonance examination may be limited to a sagittal (Tj-weighted) locator followed by two or three contig uous, axial Tj-weighted images (with or without fat suppression) through the equator of the implant after gadolinium injection. All patients in this series demonstrated peripheral enhancement patterns, which over time progressed (with variability) toward the center of the implant. This peripheral pattern was somewhat asymmetric, with an advancing edge radiating from the scierai windows and their accompanying access channels. This enhancement pattern is identical to the two previously reported12'16 histologie patterns of fibrovascular ingrowth. Progression of enhancement in this series was variable, which may be caused by differences in angiogenesis among patients. Of interest, the secon dary implants in this series showed an aggressive pattern of enhancement with successful drilling by as early as five months (Patient 2). The two primary implants (Patients 3 and 4), however, did not achieve a complete, diffuse pattern 15 and 17 months, respec tively, after implantation. Only one of the secondary implants (Patient 5) showed little enhancement pro gression after 25 months of follow-up. Although motility may be more limited clinically with secon dary implants (because of somefibrosisor atrophy of the extraocular muscles), our results indicate that the potential for vascularization certainly exists and is
AMERICAN JOURNAL OF OPHTHALMOLOGY
APRIL 1995
perhaps greater when compared with primary implan tation. Study of a larger series of patients is necessary to verify this, however. The somewhat well-demarcated, intense enhance ment encountered early after implantation repeatedly demonstrated less definition and intensity over time (Fig. 2, bottom right). An understanding of the cellular changes occurring within the interstices of hydroxyapatite may explain this finding. The biologic behavior of the surrounding bone with regard to the hydroxyapatite implanted into the maxillofacial skeleton10 and as a bone graft substi tute17 may account for the long-term imaging findings encountered in this series. Compared with the imme diate postoperative period, no marked change in either radiodensity or discreteness of the margins was seen in hydroxyapatite orthopedic implants up to 24 months postoperatively. When osseous union oc curred, a complex network of multidirectional osseous projections was seen extending into the implant pores from the adjacent osteoid tissue.10 No osteoclast or other evidence of bone résorption or remodeling was seen. Abundant vascular ingrowth was identified central to the peripheral osseous ingrowth. Interest ingly, implants that healed with a fibrous (nonosseous) union lacked bone ingrowth, which indicates that direct continuity of adjacent viable bone is a prerequisite for this process of bone ingrowth.10 Hydroxyapatite, when used as an orbital implant, may evoke a different host-tissue response. In contrast to having a direct interface with adjacent viable trabecular bone and periosteum, it is placed into a scierai shell (that undergoes résorption),12 which is subsequently embedded into the soft tissues of the orbit, without exposure to any stress or compressive forces. A similar animal model involved placement of hydroxyapatite particles into buccal soft tissues.18 Hydroxyapatite (with a rounded shape) was predomi nantly coated with mature collagen with minimal foreign-body giant-cell reaction. Histologie studies of hydroxyapatite used as an orbital implant are scarce.12,16 Fibrous tissue found at the periphery of hydroxyapatite orbital implants has been reported as dense and arranged in a lamellar pattern compared with loosefibrovasculartissue with edematous matrix seen at the advancing edge more centrally.16 These cellular changes (namely, centrally directed fibrovas
VOL.119, N o . 4
cular ingrowth with peripheral replacement by dense collagen or connective tissue) most likely account for the reduced enhancement seen with time. The purpose of imaging the hydroxyapatite im plant is to determine complete vascularity and to avoid drilling the final channel for peg placement into an avascular implant. The goal is to prevent prema ture drilling and avoid associated morbidity (and cost) of infection and implant failure. Our interpreta tion of the enhancement pattern in this series has altered surgical treatment, as final drilling for peg placement is delayed until there is a diffuse (or near diffuse) enhancement pattern. We have also demon strated an improvement in the surgical outcome when the enhancement interpretation guides surgical plan ning. Although this series was small, no cases of infection have been encountered after final drilling for peg placement. In conclusion, we have shown that the hydroxyapa tite enhancement pattern after implantation consist ently has a peripheral origin centered over the access channels and centripetal progression. This pattern is identical to histologie fibrovascular ingrowth and most likely reflects this process. In most patients, this enhancement pattern consistently showed progres sion, albeit variable. However, failure of progression has also been observed. Because of this amount of variability, we must question the efficacy of final drilling and peg placement at an arbitrarily scheduled time after implantation. Timing the peg insertion according to fibrovascular progression may prevent morbidity incurred by drilling into an implant that is not completely vascularized. In this era of cost containment, several important questions need to be asked. Is postimplant magnetic resonance imaging examination justified? Is the cost of magnetic resonance imaging less than the cost incurred by an implant aborted because of drilling that was too premature? Can imaging prevent the morbidity of postimplant infection? Certainly some patients in this series have failed to attain a diffuse enhancement pattern. Would drilling into an implant with this pattern result in an avascular channel and thus predispose to infection? Perhaps the most impor tant information that magnetic resonance imaging can provide is to identify the patients who fail to vascularize their hydroxyapatite implant completely.
MAGNETIC RESONANCE IMAGING OF HYDROXYAPATITE IMPLANTS
439
Such patients may require additional surgical inter vention to encourage this process before final drilling and peg placement.
REFERENCES 1. Roy DM, Linnehan SK. Hydroxyapatite formed from coral skeletal carbonate by hydrothermal exchange. Nature 1974;247:220-2. 2. Dutton JJ. Corallin hydroxyapatite as an ocular implant. Ophthalmology 1991;98:370-7. 3. Sartoris DJ, Gershuni DH, Akeson WH, Holmes RE, Resnick D. Corallin hydroxyapatite bone graft substitutes: preliminary report of radiographie evaluation. Radiology 1986;159:133-7. 4. DePotter P, Shields CL, Shields JA, Flanders AE, Rao VM. Role of magnetic resonance imaging in the evaluation of the hydroxyapatite orbital implant. Ophthalmology 1992; 99:824-30. 5. Ferrone PJ, Dutton JJ. Rate of vascularization of coralline hydroxyapatite ocular implants. Ophthalmology 1992; 99:376-9. 6. Mules PH. Evisceration of the globe, with artificial vitreous. Trans Ophthalmol Soc U K 1885;5:200-6. 7. Frost WA. What is the best method of dealing with a lost eye? BrMedJ 1887;1:1153-4. 8. Soll DB. The anophthalmic socket. Ophthalmology 1982;89:407-23.
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9. Shields CL, Shields JA, De Potter P. Hydroxyapatite orbital implant after enucleation: experience with initial 100 con secutive cases. Arch Ophthalmol 1992;110:333-8. 10. Rosen HM, McFarland MM. The biologic behavior of hydroxyapatite implanted into the maxillofacial skeleton. Plast Reconstr Surg 1990;85:718-23. 11. White EW, Weber JN, Roy DM, Owen EL, Chiroff RT, White RA. Replamineform porous biomaterials for hard tissue implant applications. J Biomed Mater Res 1975;6:23-7. 12. Shields CL, Shields JA, Eagle RC Jr, De Potter P. Histopathologic evidence of fibrovascular ingrowth four weeks after placement of the hydroxyapatite orbital implant. Am J Ophthalmol 1991;111:363-6. 13. Reznick JB, Gilmore W O Host response to infection of a subperiosteal hydroxylapatite implant. Oral Surg Oral Med Oral Pathol 1989;67:665-72. 14. Holmes RE. Bone regeneration within a coralline hydroxyap atite implant. Plast Reconstr Surg 1979;63:626-33. 15. Perry AC. Advances in enucleation. Ophthalmic Clin North Am 1991;4:173-82. 16. Rosner M, Edward DP, Tso MOM. Foreign-body giant-cell reaction to the hydroxyapatite orbital implant [letter]. Arch Ophthalmol 1992;110:173-4. 17. Holmes RE, Hagler HK. Porous hydroxylapatite as a bone graft substitute in mandibular contour augmentation: a histometric study. J Oral Maxillofac Surg 1987;45:421-9. 18. Misiek DJ, Kent JN, Carr RF. Soft tissue responses to hydroxyapatite particles of different shapes. J Oral Maxillofac Surg 1984;42:150-60.
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APRIL
1995