Keratoprosthesis is not covered based on benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.

 

For contracts without primary coverage criteria, keratoprosthesis is not covered due to lack of medical data attesting to the effectiveness and is considered investigational.  Investigational services are an exclusion in the member certificate of coverage.

A search of literature was completed through the MEDLINE database for the period of January 1992 through December 1995. An updated search was completed for the period of December 1995 through October 2002. No articles were identified that would change the policy statement that keratoprosthesis is considered investigational, and therefore the policy statement is unchanged. Specifically, published literature consists of small case series with limited follow-up, in part due to the rarity of the procedure.  The durability of the keratoprosthesis has not been established, and postoperative complications occur often. The American Academy of Ophthalmology has not established guidelines for either a temporary or permanent keratoprosthesis, and considers this procedure to be a rare, last resort for treatment to prevent loss of the eye.

 

A search of the MEDLINE database was performed for the period of February 2006 through July 2007. Zerbe and colleagues reported results from a mixed prospective/retrospective multicenter study of the Boston Type 1 keraprosthesis.  Thirty-nine surgeons were encouraged to mail standardized pre- and postoperative reports on their patients to a central collection site. Seventeen sites (44%) provided data on 133 patients (136 eyes). The number of patients with best-corrected visual acuity of 20/200 increased from 3.6% to 57%; 19% had postoperative vision of 20/40 or better. One hundred and nine postoperative complications were reported, with 35 occurrences of retroprosthetic membrane and 21 cases of high intraocular pressures. Pre-operatively, each eye had an average of 2 (range of 0 to 8) prior corneal transplants per eye; at an average follow-up of 8.5 months (range of 0.03 to 24), retention was reported to be 95%, with 7 failures. Limitations of this report include the short follow-up time and potential bias in the discretionary submission of data.

 

The United Kingdom’s National Institute for Clinical Excellence (NICE) concludes that, “Current evidence on the safety and efficacy of insertion of hydrogel keratoprostheses does not appear adequate for this procedure to be used without special arrangements for consent and for audit or research.”

 

The keratoprosthesis is intended for the relatively small number of patients who have lost vision and for whom a corneal transplant is not expected to result in satisfactory outcomes. Since this is considered to be a salvage procedure with no acceptable alternative treatment, comparative studies are limited/lacking. The literature review with updates through August 2009 examines the types of devices currently being tested in humans, focusing on reports that allow assessment of integration within the eye, durability, visual outcomes, and adverse events following implantation. It should be noted that patients with severe corneal damage have few treatment options to prevent blindness.

 

In 2005 Falcinielli and colleagues described a case series of 181 patients who received an osteo-odontokeratoprosthesis (OOKP) (Falcinelli, 2005). With a median follow-up of 12 years, survival analysis estimated that 18 years after surgery the probability of retaining an anatomically intact OOKP was 85% with reasonable visual acuity.

 

In 2008, investigators from Spain published a retrospective review of 227 patients who underwent OOKP (n = 145), or osteo-keratoprosthesis (OKP, n = 82) using tibial bone in patients who lacked canine teeth to assemble the prosthesis (Michael, 2008). The primary diagnosis was chemical or thermal burn, Steven-Johnson syndrome or Lyell syndrome, cicatricial pemphigoid, trachoma, and a small number of other or not assignable. Mean follow-up was 8.4 years of OOKP and 3.5 years for OKP. Anatomical success at 10 years, defined as retention of the keratoprosthesis lamina, was estimated to be 66% for OOKP and 47% for OKP. Visual acuity was measured as no light perception, light perception only, light projection, hand motion, and counting fingers. Functional success at 10 years was estimated to be 38% for OOKP and 17% for OKP.

 

Hughes et al reported vitreoretinal complications of the OOKP in a retrospective review of 35 cases performed at one hospital in England between 1996 and 2005 (Hughes, 2008). Original diagnoses were Stevens-Johnson syndrome in 15 patients, chemical injury in 5, mucous membrane pemphigoid in 3, and topical medication toxicity in 3. Follow-up at a mean 57 months (range of 13 to 105 months) revealed 9 vitreoretinal complications in 8 patients (23%). These included vitreous hemorrhage (n = 3), rhegmatogenous retinal detachment (n = 3), retinal detachment complicating endophthalmitis after lamina resorption and optic extrusion (n = 2), and intraoperative choroidal hemorrhage (1 patient). Retinal detachment with loss of vision occurred in 5 of the 8 patients. A 2009 publication of 36 patients treated at the same hospitals between 1996 and 2006 (likely to be an overlap of the patients reported by Hughes et al) estimated that the probability of retaining visual acuity was 53% at 5 years and 44% at 9 years (Liu, 2008).  In addition to the vitreoretinal complications causing loss of vision, resorption of the bony lamina to an extent causing visual or anatomical compromise occurred in 7 cases (19%).

 

In 2009, Bradley et al reported outcomes from all of the 30 eyes (28 patients) who had previously received a Boston type 1 keratoprosthesis at their institution; 6 of the eyes had been included in the multicenter study described above (Bradley, 2009).  Preoperative diagnoses were failed graft (26 eyes, 87%), chemical injury (3 eyes, 10%), and Stevens-Johnson syndrome (1 eye, 3%). Each eye had undergone an average of 2.6 prior corneal transplants (range, 0 – 7). Twenty eyes (66%) had preoperative glaucoma. Preoperative best corrected visual acuity (BCVA) ranged from 20/150 to light perception (<20/200 in 83% of eyes). At an average follow-up of 19 months (range, 1–48 months) anatomical retention of the initial keratoprosthesis was 83%, with 5 failures (corneal melting in 4 eyes and infectious keratitis in 1 eye). The number of patients with BCVA of 20/200 or better increased from 14% preoperatively to 77% postoperatively; 23% of patients achieved postoperative vision of 20/40 or better. In the 16 eyes followed up for at least 1 year, 12 (75%) achieved BCVA better than 20/200 and 4 (25%) achieved BCVA better than 20/40. The most common nonsurgical complication was retroprosthetic membrane formation, followed by increased intraocular pressure, corneal melt, infectious keratitis, endophthalmitis, progression of glaucoma, choroidal effusion or hemorrhage, vitreous hemorrhage, iris prolapse, sterile vitritis, posterior capsular opacity, high myopic refraction, hyphema, and phthisis bulbi. Keratoprosthesis replacement was performed at least once in 5 eyes.

 

Harissa-Dagher and Dohlman performed a retrospective study of 30 eyes (30 patients) with severe ocular trauma (6 mechanical trauma, 21 chemical burns, and 3 thermal burns) implanted with a Boston KPro type I prosthesis at the Massachusetts Eye and Ear Infirmary since 1990 (Harissi-Dagher, 2008).  Patients were followed up for an average of 35 months (range, 1–108 months). Anatomic success (retention of the prosthesis) was achieved in 5 of 5 of the mechanical trauma patients, 14 of 17 of the chemical burn patients, and 3 of 3 of the thermal burn patients. In addition to repeat KPro implantation in 3 patients (2 with early models), repair procedures for leaks were performed in 8 chemical burn eyes. Pre-operative visual impairment was near total, with visual acuity ranging from counting fingers to light perception. Postoperatively, 80% of patients achieved BCVA of 20/400 or better, and 53% achieved BCVA of 20/60 or better. There was some attrition in visual acuity over time, primarily from progression of glaucoma in eyes with chemical burns. The authors noted that glaucoma progression is difficult to control in these patients because of damage to the trabecular meshwork and to the retinal ganglion cell layer and nerve fiber layer, and that damage to the eye behind the cornea cannot always be diagnosed until the medium (e.g., opaque.

 

Aquavella and colleagues reported on a case series of 25 patients who received a Dohlman-Doane device (Aquavella, 2005). With a follow-up time ranging from 2 to 12 months, 20 of the 25 patients had a visual acuity of 20/400 or better, with 12 patients achieving better than 20/40 vision. There were no dislocations or extrusions, and no reoperations were required within the 2–12 month follow-up. Another retrospective study reported outcomes from a consecutive series of 50 eyes of 49 patients implanted with the Boston Type I keratoprosthesis and a donor cornea (Aldave,2009).  Patients had to meet the following criteria to be considered a candidate for keratoprosthesis implantation: visually significant corneal opacification (BCVA < 20/200); poor candidacy for repeat corneal transplantation because of a history of 2 or more failed transplantations, extensive corneal limbal stem cell failure with or without corneal vascularization and scarring, or both; and adequate visual potential for meaningful visual restoration. Exclusion criteria included: adequate potential for a successful outcome after penetrating keratoplasty; the presence of a comorbid ocular condition associated with a minimal chance of recovering meaningful vision, such as a chronic retinal detachment or near end-stage glaucoma; the presence of comorbid ocular conditions associated with an unacceptably high risk of postoperative complications, such as inadequate eyelid function, severe ocular surface desiccation, ocular surface keratinization, recalcitrant intraocular inflammation, patient inability or unwillingness to comply with the routine postoperative regimen, or a combination thereof. Of the 50 eyes that underwent implantation of the Boston KPro, 42 had a history of prior corneal transplantation, varying between 1 and 5 prior transplantations (mean of 2.3). Preoperative visual acuity was 20/200 or worse in all eyes, with vision of counting fingers, hand movements, or light perception in 42 eyes (88%). Glaucoma was present in 38 eyes (76%) undergoing keratoprosthesis implantation, and tube shunt implantation was performed simultaneously with keratoprosthesis implantation in 45% of the eyes with preexisting glaucoma. A total of 57 Boston type I KPros were implanted in 50 eyes. Two eyes were excluded due the early death of 1 patient and replacement of the type I KPro with a type II KPro in another patient. Nine of the 57 keratoprostheses implanted were removed, resulting in a retention rate of 84% during an average follow-up of 17 months (range, 3–49 months). Three of the 9 were removed in the first 6 months after surgery, and 5 were removed between 1 and 2 years after surgery. The final postoperative vision was improved over the preoperative vision in 38 eyes (79%), unchanged in 9 eyes (9%), and decreased in 1 eye (2%; from counting fingers preoperatively to light perception postoperatively). The percentage of eyes with postoperative visual acuity of 20/100 or better was 67% of 45 eyes followed up for at least 6 months (90% follow-up), 75% of 28 eyes (56%) followed up to 1 year, 69% of 13 eyes (26%) at 2 years, and all of the 7 eyes (14%) followed up for at least 3 years. In 38 eyes (76%), one or more postoperative complications developed. The most common postoperative complications were retroprosthetic membrane formation (44% of eyes) and persistent epithelial defects (38% of eyes). This detailed report provides information on visual outcomes and complications in a well-described patient population. The major limitation for this policy is the small number of subjects who were followed up for more than 6 months. Longer follow-up is needed to evaluate the net health outcome of this procedure.

 

Studies have suggested that the AlphaCor device is safe, although thinning or “melting” of the anterior corneal surface can lead to loss of biointegration (Crawford, 2002) (Hicks, 2003). This complication appears most prevalent in patients with ocular herpes, therefore the AlphaCor device is contraindicated in these patients. The percentage of eyes with visual acuity of better than 20/200 was 42% at an average 30-month follow-up (Hicks, 2003).  No additional studies with the AlphaCor were identified in the 2009 literature update.

 

The BIOKOP device is similar in concept to the AlphaCor device, in that a microporous polymer is used to promote host tissue integration. However, the results with this device have been disappointing. In one case series of 11 patients with 5-year follow-up, the authors concluded that the BIOKOP keratoprosthesis was only able to restore vision for a short postoperative period (Alio, 2004). Limited success was due to instability of the device and postoperative complications.

 

Successful development of a keratoprosthesis requires durable clarity, retention, and bioincorporation. The published literature reveals ongoing modifications of the design of the keratoprosthesis, both in terms of the optics and the techniques used for anchoring the optic in place, the surgical technique, and the postoperative management. Randomized trials are unlikely. Although patients can serve as their own controls, with comparison of pre- and postoperative visual acuity, case series are likely to remain small due to the low volume of the procedure. The largest case series focuses on the use of the OOKP prosthesis, which is not widely used in this country. Anatomical retention with the OOKP appears good, but restoration of vision is not well reported, and may not be much better than light perception or hand motion. With the Boston KPro short-term visual outcomes are promising, however, anatomical retention and visual success of this device at mid to long-term is unknown. Longer follow-up is needed to evaluate the effect of this technology on long-term health outcomes. However, this treatment modality has been proven in selected cases (that fulfill the criteria included in the coverage statement) to improve health outcomes on a short- to medium-term basis.

 

 

 

 

 

 

 

 

 

 

 A literature search was conducted using the MEDLINE database through February 2014. There was no new information identified that would prompt a change in the coverage statement. The following is a summary of the key identified literature.

 

 

 

 

 

 

 

 

A 2013 report from the Boston Type 1 Keratoprosthesis Study Group assessed retention of the device in 300 eyes of 300 patients (Cinolino, 2013). At a mean duration of follow-up of 17.1 months (range, 1 week to 6 years), 93% of the keratoprostheses were retained. The probability of retention was 94% at 1 year and 89% at 2 years. Mean survival time was 3.8 years. Risk factors for keratoprosthesis loss were autoimmune disease, ocular surface exposure, and number of prior failed PKs. Additional data on this cohort of patients were published in 2016 (Rudnisky, 2016).  Preoperative visual acuity, available for 47% of eyes was 20/1205. During a mean follow-up of 17 months (range, 1 week to 6 years), visual acuity improved significantly for 85% of eyes to a mean final value of 20/150. Median time to achieve a visual acuity of 20/200 was 1 month and this level of acuity lasted for a mean of 48 months.

 

Use of the Boston KPro has been reported in children and in patients with herpetic keratitis, autoimmune disease, aniridia, atopic keratoconjunctivitis, medication toxicity, and other corneal dystrophies (Colby, 2011). The device has a lower retention rate when used for highly inflammatory, cicatricial, and autoimmune ocular disorders. Other studies have also reported success in patients with severe ocular trauma (ie mechanical trauma, chemical burns and thermal burns) (Harissi-Dagher, 2008).

 

Also reported is use of the KPro as a primary treatment in eyes considered to have little or no chance of success with PK (Kang, 2012; Chang, 2015; Fadous, 2015). For example, in a study by Kang and colleagues, the most common preoperative diagnosis was primary or secondary limbal stem cell disease (71.4%), including chemical/thermal injury (28.6%), aniridia (23.8%), and Stevens-Johnson syndrome (4.8%) (Kang, 2012). Retention rate of the keratoprosthesis was 90.5% at a mean follow-up of 14.6 months (range, 6-36.3 months). In another series reporting on KPro as primary treatment in patients at high risk of failing PK, 37 (86%) of 43 eyes had corneal scarring with vascularization and the most common underlying etiology was aniridic keratopathy (11/37 eyes [27%]) (Chang, 2015).

 

A 2016 systematic review by Ahmad and colleagues examined studies on repeat versus Boston KPro implantation after failed PK (Ahmad, 2016). The review included studies of patients with corneal opacity who had failed 1 or more PKs, Studies were excluded if they were limited to patients with ocular surface disease. The primary outcome of interest was the proportion of patients with visual acuity (VA) 20/200 or better at 2 or more years after surgery. In a meta-analysis of 9 studies, the likelihood of 20/200 vision or better at least 2 years after repeat PK surgery was 42% (95% CI, 30% to 56%). A total of 104 eyes of 98 patients underwent KPro after failed PK surgery; 31 patients had only 1 previous PK. In a meta-analysis of data on KPro after failed PK surgery, the probability of maintaining a 20/200 or better VA at 2 years was 80% (95% CI, 68% to 88%). Among patients with a history of 1 failed PK, the probability of maintaining a VA of 20/200 or better at 2 years was 74% (95% CI, 45% to 89%). (The authors did not specify the number of patients included in the analysis of 20/200 vision at 2 years in patients receiving KPro.) In terms of complications after KPro following failed PK, at 2 years 29% of patients had elevated intraocular pressure (IOP) and 8% needed glaucoma surgery. In an analysis limited to patients undergoing KPro after 1 failed KP, complication rates were 29% and 10%, respectively (not significantly different from patients with KPro after any number of failed KPs). The authors did not report the number of patients included in the complication analyses.

 

In 2015, Odorcic and colleagues published a review of the literature on fungal infections after Boston type 1 KPro (Odorcic, 2015). The authors identified 15 relevant publications, primarily retrospective case series. Rates of fungal infections reported in these studies ranged from 0.009 to 0.02 per patient-year of follow-up. The largest case series assessed 291 eyes and the incidence of fungal endophthalmitis was 2.4% over 10 years.

 

Studies suggest that with the AlphaCor device, thinning or “melting” of the anterior corneal surface can lead to loss of biointegration (Hicks, 2003; Crawford, 2002). This complication appears most prevalent in patients with ocular herpes; therefore the AlphaCor device is contraindicated in these patients. In a case series published in 2003, the percentage of eyes with visual acuity of better than 20/200 was 42% at an average 30-month follow-up (Hicks, 2003). An additional case series with evaluating the AlphaCor device implantation in 12 patients was published in 2015 (Hoffart, 2015). After a mean follow-up of 25 months, 8 (67%) of devices were retained and mean gain of BCVA was 2.5 lines of visual acuity. The most common complication was corneal necrosis, observed in 7 (59%) patients 2 of which had a history of ocular herpes.

 

 

 

 

 

 

Annual policy review completed with a literature search using the MEDLINE database through February 2019. No new literature was identified that would prompt a change in the coverage statement.