|Year : 2005 | Volume
| Issue : 4 | Page : 235-241
Synthetic hydroxyapatite-based integrated orbital implants: A human pilot trial
Biswanath Kundu1, Mithlesh K Sinha1, Santanu Mitra2, Debabrata Basu1
1 Central Glass and Ceramic Research Institute, Kolkata, India
2 Eye Care and Research Centre, Kolkata, India
Oxide & Bio-Ceramic Section, Central Glass and Ceramic Research Institute, 196, Raja S.C. Mullick Road, Kolkata – 700 032
Source of Support: None, Conflict of Interest: None
Purpose: Orbital implants are used as fillers following enucleation or evisceration surgeries to replace the lost volume for better cosmesis and motility of the artificial eye. Over the last decade porous hydroxyapatite (HAp) implants derived from the naturally occurring corals, are increasingly used. Recently synthetic HAp-based implants have been introduced. After fibrovasculrisation they have the added advantage of being directly integrated with the artificial shell, thereby increasing the motility to a great extent. The current study, evaluated the efficacy of two different models of synthetic HAp with 75% porosity and pore sizes ranging from 100 to 300 mm.
Methods: Synthetic HAp powders were prepared with a novel wet chemical route. Two models of porous orbital implants with the characteristic designs for both evisceration and enucleation surgery were developed, characterised and implanted to consecutive 25 human subjects, 17 following evisceration, and 8 following enucleation. The postoperative performances of these implants were evaluated in respect to the degree of volume replacement (implant + prosthesis), presence/absence of lagophthalmos and lower eye-lid laxity, status of socket and fornices. Magnetic resonance imaging assessed the stability of the implants within the socket and progressive fibro-vascularisation within the porous scaffold as a function of time. Finally, motility of the implants as well as the prostheses (horizontal movements by Lister Perimeter) and subjective cosmetic results (qualitative) were also evaluated.
Results: During the 2.5 years of follow-up study, no significant postoperative complications were noticed. One case, showed an anterior implant exposure of 3-4 mm, and was managed with donor scleral patch graft and one case of conjunctival thinning was corrected by re-suturing the conjunctival dehiscence. Fourteen of the 25 patients had a very good movement of the prostheses (> 20° horizontal movement) and the other 11 patients had a fair motility (10 - 20°). The degree of volume replacement (with prosthesis) was found to be very good in 21 patients and fair in other 4 patients. All patients reported cosmetic satisfaction.
Conclusion: Synthetic HAp-based integrated orbital implants with this modified design were found clinically safe and cosmetically acceptable.
Keywords: Cosmesis, enucleation, evisceration, synthetic hydroxyapatite orbital implants
|How to cite this article:|
Kundu B, Sinha MK, Mitra S, Basu D. Synthetic hydroxyapatite-based integrated orbital implants: A human pilot trial. Indian J Ophthalmol 2005;53:235-41
|How to cite this URL:|
Kundu B, Sinha MK, Mitra S, Basu D. Synthetic hydroxyapatite-based integrated orbital implants: A human pilot trial. Indian J Ophthalmol [serial online] 2005 [cited 2019 Oct 14];53:235-41. Available from: http://www.ijo.in/text.asp?2005/53/4/235/18904
Enucleation/evisceration of nonseeing, disfigured or painful eye leaves the patient with an empty or anophthalmic socket resulting in a volume depletion of 7-7.5 cm3 from a total orbital volume of 30 cm3. Over 100 years back, Mules first introduced hollow spherical glass to fill this lost volume for cosmetic restoration. The common problems arising from anophthalmic sockets have been summarised by Tyers and Collins described in the clinical entity of 'postenucleation socket syndrome', the distinctive clinical features of ptosis/retraction of upper eyelid, deep superior sulcus, lower lid laxity and enophthalmos in 1985 though, the exact aetiopathological features were better understood only after 1990, when Smit et al . employed CT Scan to study the anophthalmic sockets. The initial case studies with glass-based implants showed a very high extrusion rate. The following years saw the use of several other materials such as gold or absestos as intraorbital implant, but were discarded due to high rejection/complication rate. ,,,,,
An ideal intraorbital implant should be very light in weight (< 2 g), simple in design and be completely buried within the sclera to eliminate chances of infection. Further, they should be chemically inert without any possibility of bio-degradation and need to be smaller than the patient's eyeball in size. In order to achieve the highest motility, the implants with direct coupling options with the prosthesis need to be located centrally within the muscle cone of the orbital socket, integrated with extra ocular muscles, and properly anchored to the orbital tissues., The hydroxyapatite (HAp) implant, meet almost all the requirements. These implants are biocompatible, nontoxic, nonreactive, and do not exhibit any significant foreign body inflammatory reaction., Further, its ability to promote fibrovascular in-growth substantiates its superiority over other materials. This offers stability of the implant and allows secondary drilling and direct coupling with the prosthesis, which eventually enhances the movement of the cosmetic shell. Nevertheless, it has also been reported that the rough surface of porous HAp derived from coral occasionally led to chronic inflammation, resulting in breakdown of the sclera and conjunctiva. The surgical technique for insertion and fixation of these implants with the extraocular muscles requires a wrapping material over it, often taken from donors' sclera. This could increase the risks of transmitting slow virus infections like human immunodeficiency virus and subsequent development of immune deficiency syndrome. The other disadvantages of the coral derived implants are their source-dependant nonreliable properties and high cost, that restricts their use particularly in developing countries. Therefore, synthetic HAp-based orbital implants are being considered all over the world as a better and effective alternative.
In the present study, synthetic HAp-based implants with modified designs were prepared for better volume augmentation. After thorough in vitro and in vivo characterisation they have been implanted in 25 human subjects without using wrapping materials. The postoperative results are discussed with special emphasis on clinical results, degree of vascularisation and subjective cosmetic rehabilitation.
| Materials and Methods|| |
Synthetic HAp powder was prepared with a novel wet precipitation route, the detail of which has been described elsewhere., The properties of the synthesised powder are outlined in [Table - 1]. Adequate amount of naphthalene granules of predetermined size range was added to the HAp powder to generate porosity and the powder mix was isostatically pressed, turned, and drilled to the specific design, dried and finally sintered in an open atmosphere electrical furnace at 12500C for 2 hours. A schematic representation of the overall fabrication technique is given in [Figure - 1].
The basic model of the orbital implants was conical in shape, which had a spherical anterior segment. At the first stage the model for the evisceration surgery was optimised and thereafter the enucleation models were developed in which two pairs of anchoring holes were provided for suturing of the eye muscles. In all the cases, the overall length of the major axis of the conical implants were maintained between 18 and 20 mm, while the diameter of anterior segment were kept about 16-18 mm [Figure - 2][Figure - 3]. These ocular implants along with the test samples prepared in the identical way, were characterised for different physical and mechanical properties. The final properties of the implants are outlined in [Table - 2].
The implants were evaluated first in vivo in animals for bio-compatibility, safety, and efficacy. For the present study, between October 2001 and February 2004, these implants were inserted in the eviscerated/enucleated orbital sockets of 25 consecutive human patients [Table - 3].
The human subjects were selected from the patients with blind/disfigured eye (with or without pain) secondary to intraocular tumours and/or trauma. The patients suffering from complex orbital trauma, secondary metastases in orbit, panophthalmitis, and other infectious diseases were excluded. Further, the patients with gross contracted socket who required secondary implantation and the ones suffering from systemic malignancy were also excluded. Both the eyes of all the patients were clinically examined in detail prior to the operations and photographed. Examination also included assessment of general health routine blood tests (sugar, haemoglobin, total and differential count, blood pressure, and electrocardiogram. Topical antibiotic drops were used in all cases prior to the operation.
Preoperatively topical antibiotics were used and surgery was performed under peribulbar anaesthesia. The evisceration included a 3600 peritomy prior to excising the corneal button and subsequent evisceration of the ocular tissues. After cleaning the scleral shell with absolute alcohol, two anterior sclerotomies at 2-8 or 4-10 O'clock position (pentagon) were made alongwith a posterior sclerotomy (circumferential with radial extensions) around the optic nerve head. An acrylic implant determined the size of the implant. The implant covered with plastic was placed into the scleral shell and the plastic was removed subsequently. The sclera was closed by overlapping manner with box mattress suture (3-0 prolene). Subsequently, Tenon's and conjunctiva were closed with interrupted 6-0 vicryl sutures and with running continuous 6-0 mersilk (horizontal/vertical), respectively. A 0.75 cm3 subconjunctival injection of gentamycin and dexamethasone was given at the end. In case of enucleation surgery, the six extra-ocular muscles were isolated, secured and disinserted after a 3600 peritomy. The optic nerve was cut and the eye-ball was removed. Subsequently, intraconal fat space was opened by enlarging the gap in the posterior Tenon's layer. 1-0 nylon were passed through the holes of the implant, knots were tied hiding inside the tunnel. Subsequently, implant was placed posterior to posterior Tenon's layer. Four rectii were fixed with 6-0 prolene suture by passing the needle through the prefixed suture loops on the implant after taking bites in the posterior Tenon's layer; inferior oblique was fixed with the inferior rectus and superior oblique with superior rectus (in selective cases). Finally, Tenon's posterior layer was partially closed which was further apposed with interrupted 6-0 vicryl sutures. A separate closure of the anterior Tenon's layer and conjunctiva were performed with 6-0 vicryl suture and with running continuous 6-0 mersilk respectively. In this case also, a subconjunctival injection of gentamycin and dexamethasone (0.75 cm3) was given at the end of surgery. All patients also received intra-operative intravenous (IV) monocef injection (1 g) and oral cefadrox (500 mg) twice daily thereafter for 1 week and oral indomethacin (75 mg) for 3 weeks.
All patients were examined on first postoperative day subsequently on weeks 1, 3, and 6 and months 3, 6, and 12. Conjunctival stitches were removed on the seventh day and generally, in the third week after satisfactory progress of the healing of the surgical wound, patients were referred to the ocularist for fitting of the molded prosthesis. Magnetic resonance imaging (MRI) of the implant was done on eight patients, 4 months after the surgery by a Signa instrument (SYS # GEMSOW of General Electric, USA) of 1.5 Tesla scanner to study the location of the implant within the orbital socket and estimate degree of fibrovascular ingrowth. Four of these eight patients were evaluated through repeat MRI study 2 months later to assess the rate of vascularisation. In all the cases, Gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) contrast was used to enhance T1-weighted fat-suppressed images, using head coil. During the imaging, the repetition time (TR)/echo time (TE) was maintained at 660/15, while the number of image matrix was kept at 192 x 256, field of view (FOV) at 230 x 230 and the slice thickness at 3 mm each in the axial planes. T1-weighted image of the implants (at 4 and 6 months after the surgery) evaluated the fibrovascular in-growth within the orbital implants. The T2-weighted image (TR/TE = 4000/87, imaging matrix 256 x 256, FOV 16 x 16, the slice thickness 3 mm) evaluated the degree of vascularisation in the axial planes of the HAp orbital implant 6 months after surgery. The degree of volume replacement (with implant and prosthesis) was measured quantitatively by exophthalmometer, while the qualitative assessment was performed by observing the upper eyelid sulcus deformity. Motility of the prosthesis was measured on the Lister Perimeter. Good motility was symmetrical horizontal movements of > 200, fair motility was movement of ³ 100 but < 200 whereas poor motility was < 100 of movement of the prosthesis. Status of the socket and fornices along with the lower eye lid laxity and the presence/absence of lagophthalmos were also studied in each patient.
| Results|| |
Twenty-one patients had a good volume replacement while the remaining four had fair volume replacement. Anterior implant exposure of 3-4 mm occurred in one patient, which was managed by donor scleral patch grafting [Figure - 4]. All patients were satisfied subjectively with the cosmetic results. [Table - 4] and[Table - 5] summarise the results of the postoperative clinical studies after the respective enucleation/evisceration surgery.
MRI with Gd-DTPA contrast-enhanced T1-weighted fat-suppressed images, using axial views, taken in eight patients 4 months after surgery showed diffuse and homogeneous intensity. Representative one such image [Figure - 5] indicated that the location of the implant within the orbital socket was perfect and was always in support of the prosthesis. Fibrovascular ingrowth (enhancement of signal intensity noted in the peripheral zone [Figure - 6] progressed towards the central lobe. The MRI images, in particular the T2-weighted images were useful for evaluating fibrovascular growth into the implant contrary to an earlier report. [Figure - 7] exhibits homogenous and distinct increase in T2-weighted image signal intensity from the implants, indicative of steady and nearly complete fibrovascular ingrowth.
| Discussion|| |
Socket reconstruction following enucleation/evisceration with the use of intraorbital implants provides better cosmesis and prosthetic motility. Porous HAp implants from the natural coral give excellent results but have certain drawbacks and are expensive. Other commercially available implants like MEDPOR (Porex Surgical, Newnan, GA, USA), derived from synthetic linear high-density polyethylene are currently under the study. In the present study we designed, synthetic HAp-based intra-orbital implants and successfully completed this human pilot study. In all the cases, the implants with conical designs and direct muscle-integrating options [Figure - 2][Figure - 3] were found stable within the orbital socket providing desired volume replacement within 5% of that of the corresponding natural eyes and cosmetic rehabilitation. A 56% (14 out of 25) of the cases had normal postoperative upper eye-lid sulcus and in no case moderate and/or severe deformity was noticed. All patients had healthy socket and adequate fornices [Figure - 8]. One patient had lagophthalmos and lower eyelid horizontal laxity, which was corrected by a Tarsal strip procedure. Four other patients also showed minor postsurgical problems, which were managed conservatively.
Although 72% of the patients had good implant motility, the identical prosthesis motility was found only in 36% cases. Remaining patients had fair prosthesis motility. This was better than two other reports., The typical shape, surface and better fibro-vascularisation probably played an important role for apparently improved motility of these implants. The synthetic HAp-based implants have been claimed to give homogenous vascularisation within 4 months of surgery but was contradicted by Sarvananthan et al ., who observed occasional patches with poor vascular in-growth attributable to inadequate interconnectivity within the pores. To overcome this problem in the present study, we used special pore formers to fabricate the implants which were evaporated in a rate controlled manner to create channel pores of adequate dimensions. [Figure - 9] presents a typical microstructure of the implant in which the inbuilt pores and their size distributions are evident. The noninvasive MRI of the implants was conducted to assess the degree of fibrovascularisation. Contrast enhanced MRI is powerful and accurate tool to understand the growth of soft tissues and study the slow blood flow and increased blood vessel dimensions., In the present study, intravenous Gd-DTPA increased the signal intensity quite significantly and improved the image quality and necessary contrast to understand the soft tissue in-growth. In eight cases where the MRI was done the soft tissue in-growth was quite adequate in the implants, probably due to typical pore morphology present in the implants. The study in four patients 6 months after surgery showed that vascularisation was more or less complete, indicated by the homogenous high intensity image of the implant.
The study also pointed out that the improved motility of the implants was not apparent in the prosthesis which was probably due to poor transmission of movement through friction. This necessitates insertion of a motility peg into the implant. Since the pegging operation is possible only after adequate fibrovascularisation within the implants, we suggest that this secondary operation may be conducted at least 6 months after the primary one. The timing and the preparation for the second surgery is controversial. Sarvananthan et al ., suggested MRI study guided timing of the secondary surgery whereas Rubin et al ., recommended simultaneous pegging surgery in HAp implant and Ashworth et al ., preferred to insert the motility couple 6 months after the primary operation. [Figure - 10][Figure - 11][Figure - 12][Figure - 13], shows almost 100% horizontal movement of the prosthesis in a patient who was inserted with a ceramic based, light weight motility peg, 6 months after the primary surgery. The pegs used in the present case were made up of a bio-inert ceramic material of biomedical grade containing > 99.7% alumina fabricated by pressing, presintering, turning and finally sintering at a temperature of about 16000C to remove the open porosities.
The present pilot study indicates that the synthetic HAp-based orbital implants are safe and cosmetically acceptable implants after enucleation and evisceration in human subjects, although further long-term and large series evaluations are necessary.
| Acknowledgment|| |
This work is financially supported by Society of Bio-Medical Technology, Defence Research and Development Organisation, Ministry of Defence, Government of India.
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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10], [Figure - 11], [Figure - 12], [Figure - 13], [Figure - 14], [Figure - 15], [Figure - 16]
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