A bioengineered corneal tissue made from purified medical-grade porcine skin collagen — a US Food and Drug Administration-approved material for medical use — has been tested in a pilot study of 20 patients with advanced keratoconus; 8 in India and 12 in Iran (ClinicalTrials.gov Identifier: NCT04653922), a report in Nature Biotechnology shows. Of the 14 who were blind at the outset of the trial due to advanced keratoconus, none were blind 2 years after receiving the implant, according to the study.
Prior research with human donor lenticules or disc-shaped tissue has shown some corneal flattening, and best-corrected visual acuity (BCVA) gains of 2 to 3 logMAR lines, investigators explain. But the bioengineered porcine tissue reached “central corneal thickness increase 10 times that of previous studies sustained for at least 2 years, resulting in 3 times the degree of corneal flattening of previous studies and a substantially greater improvement in vision.” Implantation is sutureless, and sterile packaging sustains a shelf life of at least 2 years, as verified by an accredited laboratory.
The implant, termed the bioengineered porcine construct double crosslinked (BPCDX), is a Class III medical device. Chemical and photochemical crosslinking improves its stability and strength — water soluble substances in this process are rinsed away during production. BPCDX is a clear, large diameter hydrogel, either 280 µm or 440 µm thick. With a 2 mm incision, the device is introduced into an intrastromal pocket created manually or with femtosecond laser.
The studies took into account 2 cohorts — 1 from Iran, and 1 from India. The Iranian patients included 12 participants (mean age 30.8±9.7 years, 5 women, 7 men). They had a mean central corneal thickness (CCT) of 446±66 µm and no contact lens tolerance and 6 were legally blind. In the Indian cohort, 8 patients (mean age 26.6±4.7 years, 2 women, 6 men) had a mean CCT of 378±15 µm, no contact lens tolerance, and all 8 were legally blind.
After surgery, 5 patients had a slight temporary haze — corneal transparency 3+, but clarity improved and stabilized by one week, and all participants displayed 4+ at 2 years. Also at final visit, no adverse events such as rejection, scarring, or vascularization were noted. CCT increased for all (P <.001); specifically, to 587±18 µm at the Indian site, and 728±88 µm in the Iranian cohort. Mean anterior curvature decreased from 57.1±7.0 D to 48.4±1.5 D for patients in India, and from 57.7±6.5 D to 52.8±1.9 D for those in Iran. Further, maximal apical curvature significantly fell in both groups.
Due to improved corneal curvatures, best contact lens-corrected VA was significantly better for recipients in India and best spectacle-corrected acuity for patients in Iran (both P <.001). Mean final corrected VA for Indian participants was 20/26, and for those in Iran 20/58. All 20 were contact lens intolerant before surgery, but every individual could wear lenses for normal periods at 2 years postoperative.
Investigators speculate strong results may be credited to sufficient stiffness of BPCDX to press the anterior and posterior stromal layers outwards, while holding up to intraocular pressure, which rose slightly in the Indian cohort, but remained within normal levels.
The implant addresses a concern of limited donor corneas. The current ratio of 1 donor cornea to every 70 needed for individuals with disorders such as late stage keratoconus is intensified by the global COVID-19 pandemic, and the tissue that is donated must be safety-tested and transplanted within 7 days.
This pilot did not include a control group with traditional corneal transplants, which represents a limitation, as well that selection bias may have occurred. BPCDX is so far manufactured in two thicknesses, but can be produced in non-uniform or tapered thicknesses.
Disclosure: Some [or one] study author(s) declared affiliations with the biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Rafat M, Jabbarvand M, Sharma N, et al. Bioengineered corneal tissue for minimally invasive vision restoration in advanced keratoconus in two clinical cohorts. Nature Biotechnology. Published online August 11, 2022. doi:10.1038/s41587-022-01408-w