AlphaCor: Clinical outcomes.

PURPOSE: To study the outcomes of AlphaCor implantation. METHODS: : The AlphaCor artificial cornea is indicated for corneal blindness not treatable by donor grafting. Prospective preoperative and follow-up data were collected. Data were evaluated using SPSS for statistical analysis of outcomes, trends, and associations. RESULTS: This report includes data returned through February 28, 2006, for all 322 devices implanted, with mean follow-up in situ of 15.5 months and a maximum of 7.4 years. The probability of AlphaCor retention at 6 months and 1 and 2 years for protocol cases was 92%, 80%, and 62%, respectively, and off-label cases were at higher risk (P = 0.010), as were cases not prescribed medroxyprogesterone (MPG; P = 0.001). Currently, the most common complications were stromal melting, fibrous reclosure of the posterior lamellar opening, and white intraoptic deposits, with incidences in 2005 of 11.4%, 5.1%, and 2.6%, respectively. MPG seems to protect against melts, and eyes with a history of herpetic keratitis were not at increased risk. A history of glaucoma or the presence of tubes did not affect device retention. Complications culminated in loss of an eye in 1.3%. Mean preoperative visual acuity (VA) was hand movements. The VA achieved postoperatively (light perception to 20/20) was affected by previous pathology and postoperative course, with a mean improvement of 2 lines. CONCLUSION: AlphaCor provides a treatment option where a donor tissue graft would not succeed in severe corneal conditions, while being reversible to a donor graft in the event of complications for anatomic integrity. Surgical technique and adjunctive therapies are evolving with experience. Continued data collection is important for a fuller understanding of AlphaCor's role.

Screening for drug-induced spoliation of the hydrogel optic of the AlphaCor artificial cornea.

Clinical experience and in vitro investigations demonstrated that AlphaCor, a hydrogel keratoprosthesis, can undergo both surface spoliation and internal depositions/colourations after exposure to certain medications, alone or in combination. While the most commonly used medications have not been associated with spoliation in vivo, many medications are reportedly used due to the complex co-pathologies in many recipients, and regional variations in available medications. We screened a number of drugs used or proposed by surgeons for use in AlphaCor patients to evaluate their potential to cause visually significant optic spoliation (surface or intragel, or colour changes). Poly(2-hydroxyethyl methacrylate) discs with an identical composition to AlphaCor's optic were incubated with each medication and then with simulated aqueous humour (SAH) at 37 degrees C for 7 days. They were then examined under magnification and by histology (selected samples). Clinical feedback for the test medications was reviewed and compared with the in vitro results. A minority of the drugs caused surface spoliation (TobraDex, Prednefrin Forte, Azopt) or colour staining (including Zymar, Vigamox, Quixin) when tested alone, but SAH appeared to promote hydrogel cloudiness and surface deposits. The in vitro spoliation occurred more frequently than in vivo reports of spoliation in recipients of the same medications. This study is consistent with earlier findings in demonstrating involvement of topical medications in hydrogel spoliation, although a much lower incidence of spoliation is reported for AlphaCor in human recipients than indicated by the laboratory findings. The interactions of biological fluids and drugs require further study.

Orbital implants: potential new directions.

This article reviews orbital implants used to replace an eye after enucleation or evisceration. Advantages of implant placement are described, with discussion of implant and wrap material, and design features that affect clinical outcomes. Implants may be porous or nonporous, pegged for linkage with a cosmetic shell or unpegged, and may be wrapped with a covering material or tissue or unwrapped. Device shape, volume and material qualities affect tissue tolerance and the risk of exposure or extrusion. Limitations of currently available devices are discussed, with factors affecting surgeon and patient choice. Ideally, a device should be easy to insert, avoid the need for wrapping or adjunctive tissues, be light, biointegratable, comfortable after implantation and provide satisfactory orbital volume replacement, movement and cosmesis without requiring further surgery or pegging. This review briefly discusses developments in implant design and aspects of design that affect function, but is not a detailed clinical review; rather, it aims to stimulate thought on optimal design and discusses recent developments. Novel technology in the form of a prototype device with a soft, biointegratable anterior surface is described as an example of newer approaches.

Effect of multipurpose solutions for contact lens care on the in vitro drug-induced spoliation of poly(2-hydroxyethyl methacrylate) in simulated aqueous humour.

Drug-induced spoliation of hydrogels as contact lenses or as implants in the anterior eye is a frequent occurrence in clinical practice. This study explores the capacity of three commercial multipurpose solutions for contact lens care to reduce the spoliation of poly(2-hydroxyethyl methacrylate) (PHEMA) specimens exposed to a simulated aqueous humour formulation and to three topical drugs commonly administered after insertion of artificial corneas (Predsol, Optimol and Depo-Ralovera). ReNu MultiPlus (Bausch & Lomb), Complete Blink-N-Cleantrade mark Lens Drops (Allergan) and Complete Protein Remover Tablets dissolved in Complete ComfortPLUS (both from Allergan) were evaluated. All multipurpose solutions were able to dislodge passively the deposits formed on hydrogels in the simulated aqueous and in the presence of Predsol and Optimol, but none were effective against the deposits induced by Depo-Ralovera. A reduction of the calcium content in deposits caused by Predsol and Optimol was confirmed after treatment with the protein remover preparation, while the other multipurpose solutions caused the complete removal of the deposits. In experiments designed to evaluate the preventive action of the multipurpose solutions, no such effects were observed regardless of the drug involved. The prospect of using multipurpose solutions as eye drops following implantation of a hydrogel artificial cornea is a valid alternative for reducing device spoliation, however it appears to depend on the nature of the postoperative medication.

Retroprosthetic membranes in AlphaCor patients: risk factors and prevention.

PURPOSE: To report retroprosthetic membrane (RPM) formation in association with AlphaCor and identify risk factors for their formation and strategies for prevention and management. METHODS: Review of AlphaCor data and case histories and literature review. RESULTS: RPMs occurred with AlphaCor in 14 (9.3%) cases. We find significant associations with systemic risk factors (race, hypertension, diabetes mellitus) rather than ocular history, but perioperative management may also be related to risk of RPM development. Histology demonstrates a fibrovascular tissue resembling scarred corneal tissue. Similar histologic findings have been reported for other devices. CONCLUSION: Retrocorneal membranes and RPMs with earlier keratoprostheses have frequently been reported without specific identifiable causes. Diabetes is known to be associated with intraocular membrane formation. This study demonstrates that systemic factors affect the risk of RPM formation with AlphaCor. In cases identified as at greater risk of membrane formation, peri- and postoperative therapies such as steroids, non-steroidals, heparin or rTPA should be considered. In our series, several therapeutic and surgical strategies appear effective but recognizing patients at increased risk pre-operatively and using preventive measures where indicated is likely to be key to minimizing the incidence of this complication.

A risk score as part of an evidence-based approach to the selection of corneal replacement surgery.

PURPOSE: There is currently no standardized methodology that permits preoperative prediction of the surgical technique or drug regimen for corneal grafting most likely to succeed for an individual patient. A score factor related to the chance of successful penetrating keratoplasty (PK) may assist in standardization of graft outcome reporting and evidence-based management. METHODS: The Risk Score (RS) is based on factors shown to reduce the probability of 1-year survival of conventional PK in increments, using published Australian Corneal Graft Registry data. To asses its validity, Kaplan-Meier survival curves from 156 corneal replacement surgeries, stratified by preoperative RS, were used to derive the probability of survival at 1 year for donor PK, with or without systemic immunosuppression, and for synthetic PK with the AlphaCor artificial cornea. The probability of survival was then plotted against RS for each regimen, producing a family of curves. RESULTS: The mean RS for immunosuppressed cases was higher than for nonimmunosuppressed cases. The AlphaCor group had the highest scores. AlphaCor survival is little affected by the factors that affect the risk of graft survival, whereas the probability of donor graft survival, immunosuppressed or not, is inversely related to RS. CONCLUSIONS: This study was designed to test a method that allows objective comparison of outcomes of different methods of corneal replacement for different risk categories. Analysis of this small dataset supports the validity of the concept and suggests that the Risk Score is a useful descriptive statistic. With a sufficient sample size, statistically significant evidence of the optimum management method for an individual patient with a particular risk profile could be determined such that a prospective patient's preoperative RS could be used to assist management decisions. In particular, data allowing separation of different immunosuppression regimes would be useful. Functional outcomes such as visual acuity would be more significant clinically than the survival end point used in this study and the system also could be adapted to different follow-up periods.

Two cases of AlphaCor surgery performed using a small incision technique.

The authors have evaluated the AlphaCor artificial cornea (previously Chirila KPro) in human patients since 1998, utilizing an intrastromal technique requiring extensive corneal lamellar dissection and recommending conjunctival flaps in all cases. Recent availability of low-profile instruments has facilitated a simpler technique, which was first evaluated in two subjects followed for over 1 year prior to recommending the technique for wider adoption. The new technique is presented and illustrated herein, and its benefits and limitations compared with the traditional AlphaCor implantation are discussed.

In vitro drug-induced spoliation of a keratoprosthetic hydrogel.

PURPOSE: To investigate in vitro the effects of selected drugs on the spoliation of poly(2-hydroxyethyl methacrylate) (PHEMA), a synthetic acrylic hydrogel currently used for the manufacture of a keratoprosthesis, AlphaCor. The experiments were carried out both in the presence of simulated aqueous humor (SAH) and in its absence. METHODS: Disks of PHEMA were incubated and shaken with 9 commonly prescribed drugs at 37 degrees C in sterile conditions for 1 week. Samples were incubated either in SAH only (controls), in each drug preparation, or in each drug for 1 week followed by 1 week in SAH. The drugs selected for this study were steroids (prednisolone, dexamethasone, fluorometholone, medroxyprogesterone), antiglaucoma drugs (timolol maleate and pilocarpine), and antibiotics (chloramphenicol, cephazolin, and ciprofloxacin), as commercially available formulations. Following incubation, the PHEMA specimens were examined visually and then histologically, after staining with alizarin red for the presence of calcium in the spoliating sediments/deposits. RESULTS: Although only 5 of the drug formulations (dexamethasone as Maxidex, fluorometholone as FML, pilocarpine as Isopto Carpine, chloramphenicol as Chlorsig, and medroxyprogesterone as Depo-Ralovera) induced spoliation of the hydrogel in the absence of SAH, all drugs induced spoliation after postincubation in SAH, and calcium was detected in the majority of samples. The deposits on the hydrogel specimens incubated first in cephazolin (as Cefazolin-BC), pilocarpine (as Isopto Carpine), and chloramphenicol (as Chlorsig) and then in SAH did not contain calcium, despite its presence in SAH. CONCLUSIONS: The study appears to confirm our earlier clinical observations that topical medication may play a role in the spoliation of the hydrogel ophthalmic devices. Presence of calcium in the deposits seems to be correlated to the nature of drug. Although the incidence of spoliation in real clinical situations is much lower than suggested by this extreme-case in vitro simulation, topical therapy after implantation of AlphaCor should be carefully considered, kept to the minimum required, and additive-free where possible.

Cataract surgery with the AlphaCor artificial cornea.

PURPOSE: To review the outcomes of AlphaCor artificial cornea (Argus Biomedical Pty Ltd.) implantation concurrent with or subsequent to cataract surgery. SETTING: Nonrandomized multicenter clinical trial. METHODS: AlphaCor devices were implanted under an approved protocol. Extracapsular cataract extraction with intraocular lens implantation was concurrently performed in 5 cases; an additional case had a displaced cataractous lens removed after severe blunt trauma subsequent to AlphaCor implantation. RESULTS: Cataract surgery was difficult because the view was restricted and residual soft lens matter was retained. There was an increased incidence of postoperative complications (eg, melt, glaucoma) in cataract cases compared with noncataract AlphaCor cases. The mean best corrected visual acuity was worse in cases with cataract than in cases without. CONCLUSIONS: The technique for cataract surgery in AlphaCor cases needs to be refined. Imaging studies performed postoperatively may help ascertain whether soft lens matter remains so additional antiinflammatory medication can be considered. Melting appears to be preventable by topical medroxyprogesterone 1% therapy.

Deposits in artificial corneas: risk factors and prevention.

PURPOSE: To identify risk factors for calcium deposition and pigmented staining within AlphaCor artificial corneas. METHODS: Retrospective analysis of data from 72 AlphaCor implantations was conducted. Histological analysis of explants was performed. RESULTS: Eight cases of either intraoptic calcium or pigment deposition occurred in AlphaCor patients between 2.5 and 21 months after implantation. Four cases had diffuse white deposits, confirmed to be calcium and associated with prior coadministration of topical steroids and beta-blockers. The other four cases had brown deposits, associated with cigarette smoking and topical levobunolol. CONCLUSION: These findings led to changes in patient management protocols, surgeon training and patient information so as to minimize the risk of further occurrences. No further cases of white deposition have occurred after warning surgeons of the risk associated with certain topical therapy combinations. The risk of brown staining may be difficult to remove completely as it appears that environmental exposure to chemicals may cause deposition in addition to personal smoking habits and topical medications.

AlphaCor cases: comparative outcomes.

PURPOSE: To describe clinical outcomes after a novel type of corneal surgery, implantation of an artificial cornea, AlphaCor , and to evaluate outcomes in comparison with alternative keratoprostheses and high-risk grafts. METHODS: Case reports and data from a noncontrolled clinical trial and a literature review. RESULTS: The probability of AlphaCor retention to 1 year is 80%. Postoperative best corrected visual acuity ranges from Perception Light to 20/30. The most significant complications are stromal melts and optic depositions, for both of which the main risk factors have been identified. Complications can be managed without loss of the eye. CONCLUSION: Results from the clinical trial period have helped to determine the indications and risk factors for AlphaCor surgery and to refine surgical techniques. Continued monitoring of outcomes as the series increases will allow a more accurate determination of comparative outcomes. The series provides preliminary evidence that AlphaCor may have a lower incidence of complications than traditional keratoprostheses and may prove to be preferable to a donor graft in high-risk cases.

Melting after keratoprosthesis implantation: the effects of medroxyprogesterone.

PURPOSE: This study was conducted to evaluate the effect of topical medroxyprogesterone (MPG) following KPro implantation in human subjects in whom donor tissue grafts had been contraindicated by high risk of failure. METHODS: Outcomes of implantation of the Chirila KPro, now known as AlphaCor, were reviewed with respect to postoperative MPG therapy. Ten of 45 (22%) patients had received MPG for a period of 12 months, while 35/45 (78%) had not. MPG treatment was halted because the drug is not approved as an adjunctive treatment of KPro patients. The main outcome measures were the incidence and timing of corneal stromal melting and visual acuity. RESULTS: Of those untreated with MPG, 34% developed a melt (mean follow-up 9.7 months), whereas of those who received MPG, 60% developed a melt (mean follow-up 28.4 months). However, mean time to melt onset for untreated cases was 8.8 months, whereas mean time to melt onset for treated cases was 23.2 months. There is a statistically significant association between time to melt onset, where melts occurred, and MPG therapy (chi2 = 0.001). In both groups, melts were strongly associated with a history of ocular HSV, which represented 17.1% of untreated and 20% of treated cases and is now considered a contraindication for AlphaCor. Preoperative visual acuities were in the range Perception Light (PL)-Count Fingers (CF) in all cases, whereas mean best postoperative best corrected visual acuity was 20/200 (range PL-20/30) in untreated cases and was 20/120 [range Hand Movements (HM)-20/30)] in MPG-treated cases. CONCLUSIONS: Although MPG may not influence the underlying incidence of melt-related complications, which are likely to be associated with other risk factors especially HSV, it may have a protective effect with regard to melt onset and severity. Controlled studies would assist evaluation of its use in this indication.

Outcomes of implantation of an artificial cornea, AlphaCor: effects of prior ocular herpes simplex infection.

PURPOSE: To review outcomes of AlphaCor artificial cornea implantation in patients with and without a history of ocular herpes simplex virus (HSV) and to determine whether herpetic eye disease is an indication for AlphaCor surgery. METHODS: Outcomes of the initial 40 implantations were reviewed and stratified by the presence of a history of ocular disease caused by HSV. Outcomes measures (complications, visual acuity gained) were compared. RESULTS: Eight of the 40 AlphaCor implantations (20%) were in patients with a history of ocular HSV. Six of these eight patients (75%) developed melt-related complications after AlphaCor insertion. Half of the affected patients required removal of the AlphaCor and replacement with a donor corneal graft to restore ocular integrity. In comparison, only six of the 32 (18.8%) patients without HSV developed a melt after AlphaCor insertion. Patients with HSV with devices in situ exhibited a mean loss of 0.3 line of best-corrected visual acuity compared with the preoperative visual acuity, whereas patients without HSV exhibited a mean gain of 1.4 lines of best-corrected visual acuity. CONCLUSIONS: The extensive lamellar corneal surgery involved in AlphaCor implantation may precipitate reactivation of latent HSV such that reactivation and resultant inflammation reduce device biointegration and facilitate melting of corneal stromal tissue anterior to the device. Although there may be some benefit from systemic antiviral medication, the current series is not large enough to demonstrate such a benefit, and melting can occur despite medication. The statistically significant difference in outcomes between recipients of AlphaCor with and without HSV is evidence that a history of HSV should be an exclusion factor for AlphaCor surgery.

The Chirila Keratoprosthesis: phase I human clinical trial.

OBJECTIVE: To undertake a preliminary safety and performance evaluation of an artificial cornea, the Chirila Keratoprosthesis, in human patients. DESIGN: A prospective, interventional case series. PARTICIPANTS: Fourteen consecutive patients with blindness of corneal origin not treatable by repeated standard penetrating keratoplasty. METHODS: Keratoprostheses were manufactured and implanted. The patients, all with preoperative visual acuity of light perception to count fingers (CF), were followed clinically in adherence to a protocol. MAIN OUTCOME MEASURES: Safety (keratoprosthesis retention, incidence of serious complications) and performance (visual acuity, comfort, appearance). RESULTS: Ninety-three percent of keratoprostheses were retained to the date of reporting, up to 2.5 years. One keratoprosthesis (7%) was removed in a manner that restored the patient's preoperative condition. All but one patient maintained their preoperative level of visual acuity or improved on it, with most achieving their estimated full potential visual acuity, (range, count fingers - 20/20). CONCLUSIONS: This keratoprosthesis is acceptably safe and has demonstrated an ability to restore vision in cases in which alternative management would have had a poor prognosis. More extensive trials are warranted.