Table 3.
Summary of recent evidence on CAIRS for the management of keratoconus.
| Author and Year | Study design | Case number | Follow-up | CAIRS calculation | CAIRS preparation | CXL (yes/no) | Diagnosis |
|---|---|---|---|---|---|---|---|
| Jacob et al. 2018 (46) | Prospective interventional case series | 24 eyes (20 patients) | Mean 11.6 ± 3.6 months (range 6–18) | Uniform size; same diameter/arc length for all | Trephine (double-bladed Jacob CAIRS trephine); donor corneal rims | Yes – intraoperative A-CXL or A-CACXL | Keratoconus |
| Haciagaoglu et al. 2023 (47) | Retrospective case series | 44 eyes (32 patients) | 6 months | Istanbul Nomogram (inner Ø 4 mm; outer Ø 7.5 mm; depth 200 µm; cone-guided) | Femtosecond laser tunnel (iFS 150 kHz); KeraNatural™ sterile allograft | No (deferred if progression) | Keratoconus |
| Nacaroglu et al. 2023 (48) | Retrospective case series | 65 eyes (49 patients) | 12 months | Istanbul Nomogram (inner Ø 4 mm; outer Ø 7.5 mm; −35% depth; single 160° over cone) | Femtosecond laser tunnel (iFS 150 kHz); KeraNatural® | Preoperative CXL only (mean 60.9 ± 42.1 months before) | Keratoconus |
| Jacob et al. 2023 (49) | Prospective interventional case series | 32 eyes (29 patients) | ≥12 months (mean ∼1 year) | Individual topography-guided; tapered/variable volume per Barraquer's law | Trephine + CAIRS Customizer™; donor corneoscleral rims; femto tunnel at ∼50% depth | Yes – intraoperative A-CXL/A-CACXL (31/32 eyes) | Keratoconus with decentered asymmetric cone |
| Kirgiz et al. 2024 (50) | Retrospective case series | 23 eyes (23 patients) | 6 months | Modified Istanbul (inner Ø 4.5 mm; outer Ø 7.75 mm; depth 200 µm) | Sequential trephination (8 mm → 6 mm punch); femto tunnels (VisuMax) | Partly – prior CXL in 65% (≥12 months); no simultaneous CXL | Keratoconus |
| Mazzotta et al. 2024 (51) | Case report/technical note (n = 2) | 2 eyes (2 patients) | Up to 3 months | Modified MS39–Alfonso integrated; MZ personalized nomogram | All-femtosecond laser–cut trapezoid segments; 1.5 mm wide; 300–460 µm thick | No corneal CXL; A-CXL applied to segments pre-implant | Keratoconus |
| Yucekul et al. 2024 (52) | Retrospective comparative case series | 67 eyes (47 patients) | 6 months | Istanbul Nomogram (inner Ø 4 mm; outer Ø 7.5 mm; depth 200 µm; single 160° segment) | Femtosecond laser (iFS 150 kHz); KeraNatural allograft; annular tunnel concentric to cone | 30 eyes with prior CXL; 37 without prior CXL | Keratoconus |
| Bteich et al. 2025 (53) | Observational case series (design not explicitly stated) | 20 eyes (15 patients) | 12 months | Surgeon-specific (AUBMC); optical zone 6.0 mm; depth 250–300 µm; 20% double segments | Femtosecond laser–cut (LDV Z8); donor rim in artificial AC; 500/750 µm thickness options | No (neither simultaneous nor staged) | Corneal ectasia |
| Keskin Perk et al. 2025 (54) | Retrospective case series | 62 eyes (49 patients) | Mean 23.2 ± 13.5 months (6–36); visits at 1, 6, 12, 36 months | Istanbul Nomogram (inner Ø 4 mm; outer Ø 7.5 mm; depth 200–250 µm; ∼160°; 1 mm width) | KeraNatural sterile allograft; trimmed to ∼160°; femto tunnels (iFS) | No (prior CXL and double-ring cases excluded) | Keratoconus (treatment) |
| Benz et al. 2025 (55) | Retrospective interventional case series (single-surgeon) | 17 eyes (16 patients) | Mean 141.1 ± 79.9 days (range 30–338) | Modified Istanbul; inner Ø 4–5 mm; outer Ø 7.2–8.2 mm; tunnel width 1.6 mm; depth 200–250 µm (pachymetry-guided) | Femtosecond laser (Ziemer Z6); KeraNatural sterile arc implant; OCT-guided centration; no sutures | 1 eye had prior CXL; 9 eyes underwent adjunctive CXL ≥ 1 month post-CAIRS | Keratoconus |
| Bteich et al. 2023 (66) | Interventional case series (4 eyes of 2 patients) | 4 eyes (2 patients) | 6 months | Asymmetric femtosecond laser–cut customized segments (size/shape/arc/thickness variable) | Femtosecond laser (LDV Z8) cutting on donor cornea mounted on artificial anterior chamber; proprietary software; dehydration on circular mold | No simultaneous CXL reported | Keratoconus with non-coinciding astigmatism and coma axes |
| Bteich et al. 2023 (56) | Retrospective study | 52 eyes (39 patients) | Mean 6.9 ± 5.2 months (median 5; range 3–24) | Modified PMMA-ICRS nomogram: incision on steep meridian; 1 segment for decentered cones/2 for centered; segment size 500 or 750 µm & depth 250 or 300 µm per Kmax–Kcenter/SimK/MRSE; arc length 160–170°; optical zone 5–6 mm. | Donor corneoscleral rims; epi/endo scraped; trephined (Jacob CAIRS) to 500/750 µm, bisected; mounted on 5/6 mm PVA disc; LDV Z8 femto tunnels (inner Ø 5/6 mm; outer Ø 6.8/7.8 mm; width 900 µm; depth 250–300 µm); Bowman's layer toward apex; no sutures; bandage lens. | No — stand-alone CAIRS; CXL deferred ≥ 3 months; any post-CXL data excluded. | Keratoconus (47 eyes) or corneal ectasia after laser vision correction (5 eyes) |
| Coscarelli et al. 2024 (57) | Single-arm cohort prospective study | 3 eyes (3 patients) | Mean 6.01 ± 1.02 months | Donut-shaped 360° CAIRS; femtosecond channel inner Ø 5.40 mm, outer Ø 8.00 mm; 30° angulation; 50% of thinnest pachymetry at desired location (optical zone 5.4–8.0 mm). | Donor stromal tissue from DALK remnants; double-bladed trephine 7.50 & 9.75 mm; epithelium/Descemet/Dua/endothelium removed; LDV (Ziemer) femtosecond channel; implanted 360° with McPherson forceps & Sinskey hooks; tips left near entry incision. | No — stand-alone donut-shaped CAIRS (no simultaneous CXL reported). | Keratoconus |
| Mechleb et al. 2024 (58) | Case series | 10 eyes (10 patients) | 1 month | Preop plan: depth 250 µm (regardless of thickness); 5 mm optical zone; arc length per refraction (up to 180°) with incision on steep meridian guided by refraction/coma; CAIRS thickness 400 µm for all; width per Bteich nomogram (wider in very severe KC, e.g., 1,200 µm). | Donor corneas (organ culture); FS200 femtosecond multiple concentric lamellar cuts at 400 µm using a pressurized artificial anterior chamber (200 mmHg); cuts marked for centration; annuli air-dried; tunnels created at 5 mm OZ, 250 µm depth, sized 100 µm larger than CAIRS; dehydrated segments manually inserted and positioned (Sinskey); standard postop drops. | No simultaneous CXL stated; prior CXL NR. | Keratoconus |
| Hayashi et al. 2025 (59) | Prospective case series | 5 eyes (5 patients) | Mean 6.4 ± 2.9 months | Istanbul nomogram; cone axis by CAIRSplan; tunnel inner Ø 5.0 mm; width ∼3 mm; implantation depth ∼200–215 μm; graft length to cover cone | Manual pocket (guarded knife + Hayashi CAIRS spatula); donor punched with double-bladed Jacob CAIRS trephine; AC air pressurization; Flieringa ring; iOCT; 10–0 nylon; standard postop meds | No simultaneous CXL reported; | Keratoconus (Amsler–Krumeich stage 2–4; decentered cones) |
| Mechleb et al. 2025 (60) | Retrospective observational case series | 79 eyes (71 patients) | 6 months | Depth 250 µm for all; 5 mm optical zone; arc length 90–160° per refraction/severity; incision on steep meridian (centered between coma axis and cone apex if axes differ); width by Bteich nomogram (up to 1,200 µm for Kmax > 75 D) | Femtosecond laser preparation on donor grafts (anterior lamellar mode); multiple concentric cuts at 400 µm to create annuli; air-dried; intrastromal tunnels per plan; dehydrated CAIRS manually inserted; standard postop antibiotics/steroids | NR (simultaneous/prior CXL not specified) | Keratoconus; post–corneal refractive surgery ectasia |
| Asfar et al. 2024 (61) | Retrospective cohort with propensity score matching (single surgeon, single center) | 34 CAIRS eyes (31 patients), matched 1:1 to 34 ICRS eyes | Mean 9.2 ± 4.1 months (CAIRS); visits at 1 week, 1, 3, 6, 12 months; last FU defined before any CXL | Nomogram adapted from PMMA ICRS; 1 segment (160° arc) at 6 mm OZ; segment size 500 or 750 µm based on Kmax–Kcenter/SimK/MRSE; tunnel depth 250–300 µm; incision on steep meridian | Donor corneoscleral rims (epi/endo removed); double-bladed Jacob's trephine (500/750 µm) → annuli (ID/OD 6.50/8.00 or 7.75/8.75 mm) → bisected/trimmed to 160°; LDV Z8 tunnels (inner Ø 5.8 mm; outer Ø 7.6 mm; width 900 µm; depth 250–300 µm) | No concomitant CXL; prior CXL excluded; if CXL performed later, patient exited and last pre-CXL visit used | Keratoconus |
| Jacob et al. 2025 (67) | Retrospective interventional case series (post-implantation adjustment) | 13 eyes (13 patients) | Three time points: pre-implantation, post-implantation, post-adjustment (specific months NR) | Adjustment planned from AS-OCT: modify arc length/width/thickness, reposition along channel, or optical-zone correction (e.g., reduce OZ) | Jacob CAIRS instruments; curved Y-rod/manual tunnelizer to open/free segment; reverse Sinskey for explant/re-implant; double-bladed Jacob trephine if extra segment required | 10 eyes had simultaneous CXL at initial surgery; 3 eyes had prior CXL (no CXL at adjustment) | 11 keratoconus, 1 post-LASIK ectasia, 1 pellucid marginal degeneration |
| Awwad et al. 2025 (62) | Retrospective pilot study (validation of technique) | 33 eyes (29 patients) | Up to 3 months (OCT at 1 wk, 1 mo, 3 mo) | Donor corneoscleral rims; epithelium/endothelium removed; trephined into annular rings; halved; placed in titanium mold on polyethylene drape over USB-powered cup heater (55 °C) for 5 min | Nomogram as previously described by the authors; single segment (750 µm Jacob trephine); femtosecond tunnels 5.8–7.6 mm, width 900 µm, depth 250–300 µm | No simultaneous CXL; CXL deferred ≥ 3 months; post-CXL data excluded | Keratoconus |
| Yakut et al. 2025 (64) | Prospective observational single-center study | 35 eyes (27 patients) | 12 months | Istanbul nomogram; single 160° segment; tunnel inner Ø 4.0 mm, outer Ø 7.5 mm; depth 250 µm | KeraNatural™ (ready-to-use sterile allograft CAIRS); femtosecond tunnel with iFS 150 kHz (Intralase) | NR (simultaneous/prior CXL not specified) | Keratoconus (advanced) |
| Colak et al. 2026 (65) | Retrospective case series | 6 eyes (5 patients) | 6 months–3 years (range) | Istanbul nomogram; dual opposing segments (for relatively symmetrical cones); tunnel inner Ø 4.0 mm, outer Ø 7.5 mm; depth 200–250 µm | KeraNatural (Lions VisionGift); femtosecond tunnel iFS 150 kHz; segments manually shaped; soaked in BSS before implantation | Mixed — 1 patient had prior CXL (2 years pre-op); no intraoperative CXL | Keratoconus (relatively symmetrical cones) |
AC, anterior chamber; A-CACXL, accelerated contact lens–assisted CXL; A-CXL, accelerated CXL; AS-OCT, anterior segment optical coherence tomography; AUBMC, American University of Beirut Medical Center; BSS, balanced salt solution; CAIRS, corneal allogeneic intrastromal ring segments; CXL, corneal collagen cross-linking; DALK, deep anterior lamellar keratoplasty; endo, endothelium; epi, epithelium; FS, femtosecond laser; FU, follow-up; ID, inner diameter; ICRS, intracorneal ring segments; iOCT, intraoperative optical coherence tomography; KC, keratoconus; Kcenter, keratometry at the corneal center; Kmax, maximum keratometry; LASIK, laser-assisted in situ keratomileusis; mo, month; MRSE, manifest refraction spherical equivalent; MZ, Mazzotta–Zagari; NR, not reported; OCT, optical coherence tomography; OD, outer diameter; OZ, optical zone; PMMA, polymethyl methacrylate; postop, postoperative; preop, preoperative; PVA, polyvinyl alcohol; SimK, simulated keratometry; USB, universal serial bus; wk, week.