| ◄▬ | Miragel Complicaties | ▬► |
| Marin ea 1992 | Reactie MIRA Inc. | Weerwoord Marin cs |
| Uit de handel genomen | Hwang ea 1997 | Crama en Klevering 2016 |
| Rubinstein ea 2016 | Roldan-Pallares 2016 |
1992 Marin, Tolentino, Refojo en Schepens
In januari 1992 verscheen het artikel van Marin, Tolentino, Refojo en Schepens van het Eye Research Institute in Boston, MA, 'Long-term Complications of the MAl Hydrogel Intrascleral Buckling Implant' (Arch Ophthalmol-Vol 110, January 1992). Daarin werden voor het eerst de lange-termijn-complicaties beschreven van de "MAI hydrogel intrascleral buckling implant", die 7-11 jaar na de operatie optraden.
Zeven van de 82 patiënten, bij wie de MAI plombe intrascleraal was geplaatst, kregen complicaties vanwege de zwelling van de plombe.
Geadviseerd werd om periodieke lange termijn controles te houden bij patiënten die met de MAi implant waren geopereerd:
De door Marin ea waargenomen complicaties werden in hun artikel gedetailleerd beschreven onder 'REPORT OF CASES'. Zij varieerden van een zichtbare goedaardige uitstulping onder de conjunctiva tot erosie en verschuiving van de implant het oog in. "Eventually, the swollen implant protruded en eroded trough the diseased or scarred scleral bed into the vitreous cavity".
De auteurs vermeldden dat de MAI implant aanvankelijk op basis van experimenten bij dieren en de toepassing bij 82 ogen van 79 patiënten, die waren gevolgd van 6 tot 53 maanden na die toepassing, was beschouwd als veilig en goed te verdragen, voordelen biedend boven de gangbare plombes, met minimale risico's.
Zij constateerden nu echter dat de MAI implant in 7 (8,5%) van 82 gevallen in een periode van 7 tot 11 jaar na de toepassing complicaties veroorzaakt had als gevolg van de zwelling van de implant.
Zij hadden de oorzaak van de zwelling onderzocht en geconstateerd dat deze lag in de chemische verandering van de polymeren, waaruit de hydrogel was gevormd:
Micro-Fourier transform IR spectroscopy (Figure) confirmed the occurrence of chemica! changes within the polymer. The presence of carboxylic groups implies ester hydrolysis, which may have led to structural instability. The ionized carboxylic groups result in a hydrogel that absorbs more water than the original polymer. The implant swelled and changed from opaque, soft, spongy, whitish, and compact to translucent, gel-like, cream-colored, and friable. Eventually, the swollen implant protruded and eroded through the diseased or scarred scleral bed into the vitreous cavity. ( ... )
De auteurs wezen er op dat de MAI implant de voorloper was van de MIRAgel implant die ten tijde van het publiceren van het artikel gebruikt werd. De MAI en MIRAgel implant hadden de zelfde chemische samenstelling.
Direct al in het abstract van het artikel werd gewaarschuwd m.b.t. de MIRAgel implant:
Abstract:
lt is possible that the present-day MIRAgel implant, which has the same composition as the Mai implant, may require similar precautions.
Evenals verderop in het artikel:
The MAI implant is the precursor of the present-day MIRAgel; they have the same chemical composition. Hence, potential problems related to swelling of the implant exist and warrant diligent, periodic follow-up of patients for a long time after surgery.
De auteurs vermeldden wel dat voor zover hen bekend soortgelijke complicaties niet waren gemeld bij episcleraal toegepaste implants. Zij hadden zelf de MIRAgel implant episcleraal toegepast sedert 1986 en dergelijke complicaties niet waargenomen:
However, to our knowledge, similar complications in patients who receive an episcleral implant have not been reported. We have used MIRAgel as an episcleral implant in a large number of patients since 1986 and have not observed such complications.
NB. De termijn, waarna de hydrogel implant bleek te kunnen gaan zwellen, 7- 11 jaar na toepassing ervan, was in januari 1992, toen Marin's artikel verscheen, dus nog niet verstreken.
De R&D directeur van de fabrikant MIRA Ine., Randy Hasslinger, reageerde direct in hetzelfde nummer van Arch Ophthalmology Vol. 110, Juanuary 1992 .
De bij patiënt 3 verwijderde plombe was onderzocht door MIRA Inc. en vergeleken met partijen hydrogel implants van verschillende ouderdom. De verwijderde implant had een beduidend afwijkende polymeren-structuur, maar dat betekende nog niet dat die vervorming bij de patiënt was ontstaan ("but this does not imply that the clinical specimen degraded in vivo"). Deze implant kwam namelijk uit een experimentele laboratoriumpartij van eerdere datum dan de partijen hydrogel implants van Mira Inc., en dat zou de afwijkende structuur kunnen verklaren. Van die experimentele partij bestond geen specimen meer, zodat geen verdere controle meer mogelijk was. De originele structuur van de verwijderde implant kon niet worden vastgesteld.
Er waren geen complicaties vastgesteld bij patiënten bij wie MIRAgel implants waren toegepast. MIRA Inc. bleef daarom MIRAgel produceren.
Weerwoord Refojo, Tolentino, Marin en Schepens
Refojo, Tolentino, Marin en Schepens repliceerden direct, ook weer in hetzelfde nummer van Arch Ophthalmology Vol. 110, Juanuary 1992.
Inderdaad waren ongebruikte MAI polymeer implants van dezelfde ouderdom als die van de bij de patiënten verwijderde implants niet meer voorhanden.
De verwijderde implants waren gemaakt voordat MIRA Inc. de licentie verkreeg van het Eye Research Institute om MIRAgel te produceren.
Maar MAI polymeer, vervaardigd volgens dezelfde procedure als de verwijderde implants, en de beschikbare MIRAgel implants hadden dezelfde chemische samenstelling, wat was gebleken uit de identieke "micro-Fourier transform infrared spectra".
De auteurs beschikten niet over gegevens om de mening van Hasslinger te onderschrijven dat de afwijkende structuur lag aan een experimentele laboratorium MAI partij.
In fact, there are no data available to us to support Mr Hasslinger's remark that the early MAI “laboratory batches were experimental and known to contain variable levels of components that would account for the differences described by the spectra”. Sterile MAI implants stored in saline solution in the laboratory for several years maintained their original hydration and chemica! structure. The changes were only observed in retrieved intrascleral MAI implants.
De Miragel plombe is in 1995 vanwege de complicaties door MIRA Inc. uit de handel genomen, zo blijkt uit meerdere bronnen: Lane ea 2001, Oshitari ea 2003, Kearney ea 2004, Chung ea 2004, Mazzoli ea 2004, Mears ea 2014, Rubinstein ea 2016. De memorie in verwijzing na cassatie § 109 blz. 47/48 geeft een overzicht met citaten.
In 1997 publiceerden Hwang ea, 'Hydrogel Exoplant Fragmentation 10 Years After Scleral Buckling Surgery' (Arch Ophthalmol Vol 115. Sep 1997 1205), het eerste geval van de lange termijn complicaties van de Miragel plombe.
Zij beschrijven de ontwikkeling van de MAI plombe en de MlRAgel plombe, de aanvankelijk positieve verwachtingen en de latere negatieve ontwikkelingen.
Materials used for scleral buckling procedures in detachment repair have evolved from absorbable issues, including autogenouss fascia lata and cadaveric sclera or dura mater, to nonabsorbable ynthctic agents such as polyethylene tubing, solid silicone rubber, silicone sponges, and hydrogels. Hydrogels are hydrophilic materials formed from 3-dimensional polymer networks. The most widely sed hydrogel is co-poly(methylacrylate-2hydroxyethyl acrylate), or MIRAgel (MIRA, Waltham, Mass). The forerunner of MIRAgel, MAI, has the same chemical composition. HydrogeIs are permeable to water and low- molecular-weight hydrophilic substances. Their ability to absorb and then slowly release water-soluble antibiotics offers an advantage over silicone. Ho et al 1 reported that the MAI implant was as effective a buckling element as either solid silicone rubber or silicone sponge. He noted that the degree of swelling of the exoplant could be altered by varying its state of hydration, Îts softness and elasticity were protective against erosion, and it was less prone to infection because of its laek of dead spaees and its ability to absorb, then gradllally release antibiotics.
The apparent effeetiveness and safety of MAI hydrogel scleral exoplants was reported by Tolentino et al who followed up 82 eyes of 79 patients for 6 to 53 months and found no complications of buckle extrusion, erosion, or infection. However, with longer follow-up of 7 to 11 years, 7 complications of MAI exoplants were documented by Marin and colleagues. Clînical manifestations ranged from benign subconjunctival buIging to intraocular erosion aud migration of the exoplant. At the time of surgery, the exoplants were seen to be translucent, gel-like, and friabie. Erosion into thc vitreous cavity occurred in 1 case and was complicated by difficulty grasping the friable buckle material. Micro-Fourier transform infrared spectroscopic analysis of 2 recovered implants demonstrated hydrolytic degradation of the implant leading to swelling significantly greater than the original polymer. We report the first case, to our knowledge, of scleral buckle extrusion and fragmentation associated with a MIRAgel episcleral cxoplant.
Dit geval van complicaties als gevolg van de MlRAgel plombe kon volgens de auteurs geen verrassing opleveren gezien de door Marin eerder gerapporteerde gevallen van MAl-complicaties.
This case represents the first reported breakdown of a MIRAgel sderal buckle. lts occurrenee should not be surprising, as cases of complications with the MAI exoplant,composed of the same hydrogel material, have been reported in the past. The mechanism of fragmentation and degradation likely resembles that reported with the MAI exoplant; hydrolysis of the material with resultant swelling. The presence of an incomplete capsule surrounding the buckle in our patient may have facilitated access of orbital fluid to the exoplant. Similar to the report by Marin et al,3 these changes appeared approximately 10 years after exoplant placement.
Hwang ea benadrukken de noodzaak om te anticiperen op mogelijke verbrokkeling en zwelling van de plombe.
The findings in this patient illustrate the need to anticipate potential friability and swelling of MIRAgel buckle material and to meticulously scarch for fragments during removal of long-standing exoplants.
Zij zien geen werkelijke voordelen van toepassing van de MAI en MIRAgel plombes in vergelijking met siliconen plombes.
Our observation together with the historical data suggest that there are no real advantages of MIRAgeI and MAl over silicone for use as scleral buckling materiaL
Daarna is een lange reeks artikelen verschenen, waarin eveneens de complicaties bij de Miragel scleral buckle werden beschreven. Onder meer:
In hun artikel van 2016 'The Removal of Hydrogel Explants, An Analysis of 467 Consecutive Cases' (Ophthalmology Volume 123, Number 1, January 2016) vermelden Crama en Klevering de aanvankelijke voordelen van de in 1985 ontwikkelde Miragel plombe. Na een aantal jaren werd echter een ernstig materiaalgebrek ("serious flaw") ontdekt. De oorzaak bleek te zijn de hydrolytische afbraak van het MIRAgel materiaal ("hydrolytic degradation of the MIRAgel material").
In 1985, an episcleral hydrogel explant (MIRAgel, MIRA Inc., Waltham, MA) was introduced as an alternative to silicone explants for the treatment of rhegmatogenous retinal detachment.1 The original explant (in its original shape and dimensions) is shown in Figure 1. This episcleral buckle originally seemed promising for 2 main reasons. First, the material’s soft, pliable characteristics have the potential to minimize scleral erosion. Second, the explant can absorb and then release antibiotics, thereby helping to prevent postoperative infection. Despite these potential advantages, after several years a serious flaw was discovered in the material. Specifically, hydrolytic degradation of the MIRAgel material causes progressive swelling of the explant, which can lead to strabismus, ptosis, scleral erosion, conjunctivitis, and infection around the buckle; in addition, significant cosmetic problems also can arise.2-8
Nt.2. Marin JF, Tolentino FI, Refojo MF, Schepens CL. Long-term complications of the MAI hydrogel intrascleral buckling implant. Arch Ophthalmol 1992;110:86–8.
De auteurs vermelden de meest voorkomende symptomen, die leidden tot de operatieve verwijdering van de MIRAgel plombes.
The symptoms that led to the surgical removal of MIRAgel explants in our series are consistent with previous reports. The most commonly reported symptoms were pain or discomfort (in 70% of cases), cosmetic problems (49%), eye motility disorders (39%), diplopia (29%), periocular infection (27%), and extrusion of the explant (26%). Most patients experienced a combination of these symptoms.
Het artikel van Rubinstein ea, 'Globe Loss From Intraocular Invasion of MIRAgel Scleral Buckle Components' (Ophthal Plast Reconstr Surg 2016;32:329–332,) geeft een overzicht van alle in de literatuur gevonden 'serious', 'severe complications':
The hydrogel scleral buckle for rhegmatogenous retinal detachments was first introduced in 1979 as the MAI (methyl acrylate-2-hydroxyethyl acrylate) implant and later popularized by the chemically equivalent MIRAgel implant (Mira, Inc., Waltham, MA, U.S.A.).1,2 The material has been associated with uncommon, but serious, complications. A large study of 386 patients with hydrogel scleral buckles found that 1.3% of cases required explantation.2 Other severe complications include implant expansion and fragmentation,3–5 orbital pseudocellulitis,6 orbital pseudotumor,6–9 diplopia,3,4,7,8 ptosis,3 anterior erosion through the orbital septum and orbicularis oculi muscle,10 spontaneous expulsion from the eye,11 and infection of the scleral buckle.12
Scleral erosion and intraocular penetration of the scleral buckle may also occur, potentially resulting in endophthalmitis and/or necessitating removal of the buckle and surgical closure of the scleral defect.1,5,13–17 In a large review of 38 eyes with MIRAgel buckles, Le Rouic et al.18 identified 2 eyes with scleral bed necrosis and 2 eyes that perforated during removal. Case reports and small case series in the English language literature describe a total of 11 eyes with scleral bed erosion with and without intraocular invasion. 1,5,13–17 In these cases, surgical correction was performed 8 to 20 years after MIRAgel implantation and resulted in visual acuity ranging from 20/25 to no light perception. To the author’s knowledge, the English language literature does not describe a patient requiring removal of a blind, painful eye with intraocular MIRAgel.
Rubinstein ea signaleren dat patiënten blijven komen met de meest ernstige complicaties ('blind and painfull eye', scleral intrusion'), ook al zijn de Miragel plombes in 1995 van de markt gehaald:
Although MIRAgel scleral buckles were removed from the market in 1995, patients continue to present with the most severe complications (e.g., blind and painful eye, scleral intrusion) related to the MIRAgel implant many years following placement. In this report, the authors demonstrate the clinical findings of this grave consequence of MIRAgel implantation and describe a surgical approach to treat this complication.
Leek lange tijd het beleid te zijn om Miragel alleen te verwijderen ingeval van symptomatische klachten, het advies van Roldan-Pallares ea 2016 in 'MIRAgel: the immunohistochemical expression of CD3, CD34, and CD68 in the surrounding capsule' (Eye 2016 30, 1381–1388) om alsnog alle Miragel plombes te verwijderen omdat gefragmenteerde Miragel door het menselijk immuunsysteem wordt gezien als vreemd lichaam, hetgeen lokaal ziektes veroorzaakt en bestendigt:
Abstract conclusions The immunohistochemical analysis revealed that the immune system is able to identify the fragments of MIRAgel (after its hydrolytic degradation) as a foreign body during a delayed T cell-mediated immune response. The phagocytosis by macrophages likely triggers and perpetuates local disease. Removal of MIRAgel explants before hydrolysis should be considered.
Discussion (p.1386-1387)
(...) We can assume that swelling is something that probably is already ongoing in all cases at some point after 5 years of time. The mean implantation duration of our patients was 18.5 years (range, 16–24 years) and all the patients showed clinical pseudotumor caused by MIRAgel swelling because of hydrolytic degradation. Anyway, at the moment all the implanted patients must have MIRAgel for 16 years or more (MIRA Inc. discontinued MIRAgel in 1995 in USA,39 but MIRAgel continued to be distributed outside the United States and we used it until the year 2000 10). Then, removal of MIRAgel explants before hydrolysis and probably removal of all MIRAgel explants should be considered in order to avoid complications. A significant determination coefficient (r2= 0.1933, P=0.0105) was found in our series between CD3 number (higher risk) and longer duration of MIRAgel. The immunohistochemical analysis revealed that the immune system is able to identify the fragments of MIRAgel (after its hydrolytic degradation) as a foreign body during a T cell-mediated immune response.
Summary
What was known before
MIRAgel is a scleral buckling material used in retinal reattachment surgery. Swelling and fragmentation 7 to 10 years after implantation with orbital discomfort and diplopia led to the discontinuation of its use in 1995.
Prompt removal of the MIRAgel explants was recommended when discomfort and/or fragmentation begins.What this study adds
The immunohistochemical analysis revealed the immune system is able to identify the MIRAgel fragments as a foreign body during a delayed T cell-mediated immune response. The phagocytosis by macrophages likely triggers and perpetuates local disease. Thus, MIRAgel material should be removed before hydrolysis and fragmentation in all cases.
Eyes with MIRAgel implants in place should undergo continued surveillance for ocular complications
NB. De zwelling en de fragmentatie vormen een langzaam maar niet te stoppen proces.
Ratner ea, `Biomaterials Science: An Introduction to Materials in Medicine, Edition 2, Academic Press, 2004, p.416 rk
Very little speculation has been provide in published articles about the mechanism of failure of acrylate scleral buckling devices other than that chemical degradation has occurred (Roldan-Pallares, et al., 1999). I suggest that a likely mechanism involves hydrolysis of the ester side groups enhanced by the hydrophilic nature of the polymer (as contrasted to hydrophobic polymers such as PMMA). Hydrolysis of either of the two acrylate esters in the polymer chain provides an acrylic acid moiety. Linear poly(acrylic acid) is fully water soluble and each hydrolytic event renders the polymer more hydrophilic and subject to enhanced swelling. This process is slow but inexorable in the case of the scleral buckle device.
Zie verder het overzicht in 'Miragel artikelen'.
12-6-2024
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