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Review Article

Bowman Layer Transplantation—A Review

Parker, Jack S. MD, PhD∗,†; Dockery, Philip W. MD, MPH; Melles, Gerrit R.J. MD, PhD†,§,¶

Author Information
Asia-Pacific Journal of Ophthalmology: November-December 2020 - Volume 9 - Issue 6 - p 565-570
doi: 10.1097/APO.0000000000000336
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The cornea's Bowman layer (BL) is an attractive target for transplantation. As a discreet layer, it can be isolated—and therefore harvested—from the underlying anterior stroma. BL is mechanically strong, yet thin and light and may be held in place without sutures or glue.1,2 And because the layer is acellular, BL transplantation poses minimal risk of allograft reaction or graft rejection.3,4

These peculiar advantages render BL transplantation an intriguing prospect, particularly because there seem to be an abundance of ocular pathologies that involve BL fragmentation or loss, for example, keratoconus, postrefractive scarring, Salzmann nodular degeneration, and so on.5–7

Isolated BL transplantation was first described for the treatment of postrefractive corneal haze in 2010.8 Since then, the operation has been modified for a variety of corneal conditions in which BL destruction plays a role. This manuscript provides a review of these operations and examines their published results.


BL is a thin swath of modified stroma positioned just below the epithelial basement membrane. Approximately 10 μm thick, BL is strong, acellular, and firmly adherent to the underlying anterior stroma.9 Similar to the stroma, it consists principally of types I and V collagen, although its fibers are smaller in caliber and more randomly arranged.10,11 Somewhat unexpectedly, the purpose of this structure remains, to date, unknown.

Theoretically, the BL may function as a barrier to the passage of bacteria or viruses through the cornea and into the eye.12 Focal loss of BL permits aberrant epithelial-stromal interaction, which is evident in the fibrous scars that frequently form at those sites.13,14 In addition, BL may also have some structural roles in maintaining the shape and tectonic support of the cornea because BL degeneration is evident in advanced cases of KC.15,16

However, because the deliberate and widespread ablation of BL by laser refractive surgery only rarely destabilizes the corneal architecture, the structural purpose of BL is more elusive and remains poorly understood.17

Because BL exists as an independent structure, after removing the overlying epithelium, it may be peeled as a single sheet from the underlying cornea, after which it reliably scrolls into a single or double roll secondary to the inherent elasticity of the tissue itself.


Two strategies have been described for the preparation of isolated BL grafts: manual stripping and femtosecond laser ablation.8,18 For manual stripping, the epithelium is debrided, 0.06 trypan blue (VisionBlue; DORC International) is dripped over the surface, and the cornea is lightly scored just inside the limbus, 360 degrees around, using a 30-gauge needle. Nontoothed forceps are then used to grasp the BL cut edge and peel it from the underlying stroma. Groeneveld-van Beek et al published results of manual BL preparation using whole globes and corneoscleral buttons with endothelium unsuitable for transplantation.18 They reported a 70% success rate (51/72 attempts), with all of the unsuccessful attempts failing due to either tears in the BL (19/21 failures) or inability to isolate the BL from anterior stromal remnants (2/21 failures) (Fig. 1).

Surgical views of a Bowman layer (BL) graft preparation. A donor globe is mounted on a globe holder, or a donor corneo-scleral rim is placed on an artificial anterior chamber with its epithelial side up. Corneal epithelial cells should be removed, after which, (A) just within the limbal area a superficial incision can be made over 360° with a 30G -needle. B, A peripheral donor BL edge is then lifted from the underlying anterior stroma using a single tip of a McPherson forceps. C–E, Subsequently, by grasping the BL edge with the McPherson forceps via gentle slow movements in a circular manner, the entire BL is carefully peeled away to free the tissue from its underlying attachments. After preparation, the BL graft is evaluated and can be trephined if needed. F, The BL graft tends roll into a single or double roll owing due to tissue elasticity (reprinted from Dragnea et al27 with permission from Eye and Vision).

Preliminary evaluation of femtosecond laser preparation of isolated BL grafts has also been performed. Parker et al19 described a pilot study in which 10 BL grafts were prepared: 5 via manual stripping and 5 via femtosecond ablation. The ultrastructural features were then compared using light and transmission electron microscopy. Manually stripped grafts were thinner (∼11 μm) but featured shaggy stromal remnants; femtosecond grafts were thicker (∼37 μm) but displayed smooth-cut posterior surfaces. A comparison of the optical performance of these grafts awaits in vivo trial.20


Isolated BL transplantation was originally described in a case report for the treatment of persistent subepithelial haze after photorefractive keratectomy (PRK).8 Haze after PRK may stem from dysfunctional wound healing, i.e. abnormal epithelial-stromal communication caused by the ablation of BL.6,13,14 Theoretically then, BL transplantation may reestablish the physiologic barrier between the epithelium and anterior stroma, thereby removing the trigger for scar formation.

Lie et al8 reported results of one eye with post-PRK haze (refractory to conservative treatments including repeat laser ablation) operated with isolated BL transplantation. Without first debriding the recipient epithelium, a femtosecond laser was used to create flap underneath the patient's anterior stromal scar, an isolated BL graft was positioned underneath, and then the flap was replaced, but with 1 edge folded over into the interface to encourage epithelium to migrate from the flap's surface onto the donor BL. After 2 weeks, the flap was amputated, revealing a completely reepithelialized donor BL graft, sitting atop clear/unscarred anterior stroma. With a scleral contact lens, best-corrected visual acuity improved from 20/40 (0.5) before the procedure to 20/18 (1.2) by 6 months after transplantation. No intra- or postoperative complications were noted.

This report was the first to describe the process of isolated BL graft harvest and established the technical feasibility (if not the efficacy, in the absence of a control study) of BL transplantation for the treatment of corneal disease.


An often-encountered feature of advanced keratoconus (KC) is the fragmentation of BL, which is a mechanical insult that may critically weaken the cornea and predispose it to ongoing ectasia. Therefore, the reestablishment of strong structural support in the form of an isolated BL transplant may theoretically reinforce the corneal structure and inhibit further disease progression.

In 2014, van Dijk et al21 was the first to describe isolated BL transplantation for the treatment of advanced, progressive KC with contact lens (CTL) intolerance. Ten eyes of 9 patients underwent BL “inlay,” in which isolated donor BL grafts were implanted within manually dissected, mid-stromal pockets in the recipient corneas (Fig. 2). By 6 months postoperatively, mean maximum corneal curvature (Kmax) had decreased from 74.5 diopters (D) to 68.3 D, which seemed stable through the first 12 months of follow-up. Functionally, this led to a restoration in CTL tolerance in all operated eyes. No intra- or postoperative complications were reported. Therefore, van Dijk et al proposed that isolated BL inlay grafting may be a viable option to flatten and stabilize advanced, progressive KC with few risks of complications.

Intraoperative video-stills of a Bowman layer (BL) transplantation. A, Scleral tunnel incision and (B) paracenteses are made. C, Then, the anterior chamber is filled with air, and (D–F) a manually dissected mid-stromal pocket is created, using different sizes spatulas. F, As an indication for the dissection depth, the “thin black line" alongside the spatula can be used. After removing most air from the anterior chamber, (G, H) the BL graft is inserted into the pocket atop of a glide, and (I) then carefully unfolded and centered with an 30G- cannula. J, After complete unfolding and positioning, the BL graft is sandwiched between the anterior and posterior stromal layers. No sutures are necessary to fixate the graft or to close the tunnel incision (Reprinted from Dragnea et al,27 with permission from Eye and Vision).

In 2015, van Dijk et al22 updated these results with a larger cohort and evaluated over a longer period: 22 eyes of 19 patients with advanced, progressive KC underwent BL inlay and were followed for a mean of 21 ± 7 months. Two eyes experienced inadvertent posterior perforation during manual mid-stromal dissection, and the operations were aborted. For the remaining 20 eyes, mean Kmax declined from 77.2 ± 6.2 D to 69.2 ± 3.7 D by 6 months postoperatively and remained stable thereafter. No additional intra- or postoperative complications were noted, including no cases of allograft reaction or graft rejection.

After this report, general interest in BL transplantation began to emerge. In 2016, Luceri et al23 described a series of optical changes after BL inlay grafting for KC. In 15 eyes evaluated for 12 months, observations were made regarding best spectacle corrected and CTL corrected distance visual acuity, corneal densitometry, and higher order aberrations. The most important findings were that BL inlay grafting tended to modestly improve spectacle (but not CTL) corrected visual acuity, and that this could be attributed to a reduction in corneal higher order aberrations, especially spherical aberration, after surgery. Corneal densitometry (a measurement of corneal backscatter/haze) modestly increased after BL implantation, which may reflect the incorporation of extra stroma into the donor tissue.

In 2017, Blasberg et al24 reported the first BL inlay for KC in Germany, performed in a 16-year-old with advanced, progressive disease. They observed significant corneal flattening with restoration of comfortable CTL wear, consistent with previous publications.

In 2019, Garcia de Oteyza et al25 described an additional 2 cases of BL inlay grafting for KC, but with the use of a femtosecond laser to create the mid-stromal pocket. From these 2 pilot cases, they speculate that femtosecond dissection may permit safer, faster, and more predictable pocket creation, while also lowering the risk of inadvertent stromal perforation.

Another proposed method for increasing the safety of pocket creation for BL inlay grafting was described by Tong et al in 2019.26 They reported the use of intraoperative optical coherence tomography (iOCT) to facilitate manual stromal dissection, which may theoretically enable better depth discrimination. The results of 21 eyes of 21 patients undergoing iOCT facilitated BL inlay grafting for KC were reported. With iOCT, the incidence of stromal perforation was 2/21 (10%), which is identical to that reported in initial BL studies in which iOCT was not employed.

Meanwhile, data have continued to mature from the original cohort of the first-worldwide patients to undergo BL inlay grafting for KC. After 5 to 7 years of follow-up, 84% of operated eyes continue to show a positive treatment effect: stable disease without evidence of progression and persistent corneal flattening compared to preoperative baselines (Fig. 3).27–29 Therefore, limited evidence seems to support the conclusion that isolated BL inlay grafting may be a reasonable alternative to penetrating or deep anterior lamellar keratoplasty (PK and DALK, respectively) for patients with advanced, progressive KC.

Pre- and post-operative clinical images of an eye that underwent Bowman layer (BL) transplantation. A–F, Slit-lamp pictures, (G–I) anterior corneal topography, and (J–L) posterior corneal elevation maps of an eye, (A, D, G, J) before and (B, E, H, K) at 1 month and (C, F, I, L) 5 years after BL transplantation. Slit-lamp imaging demonstrates (A) a clear cornea preoperatively, and postoperatively at (B) 1 month and (C) 5 years, whereas (E, F) the BL graft is visible as a thin white line within the host stroma (white arrows). G–I, Corneal topography shows a flattening from (G) preoperatively to (H) the 1-month follow-up, and (H–I) stabilization thereafter. Likewise, (J–L) a decrease in posterior corneal elevation can be noticed from (J, K) before to 1 month postoperatively, after which (K, L) no changes occur up to 5 years after BL transplantation (reprinted from Dragnea et al,27 with permission from Eye and Vision).

Finally, the results of a parallel study have also matured: in 2018, Birbal et al30 reported the results of 15 eyes with advanced, progressive KC that went manual, mid-stromal dissection alone (without BL inlay grafting). After a mean follow-up of 6.6 ± 2.4 years, 55% of operated eyes with Kmax <60 D showed corneal stability, whereas no eye operated with a preoperative Kmax >60 D showed corneal stability. This suggests that, to arrest the progression of severe KC, manual stromal dissection should be accompanied by BL grafting.


Despite the encouraging results of BL inlay grafting, an impediment to widespread adoption of the technique remains the persistent impression that the operation is technically challenging. In addition, there is a theoretical objection that mid-stromal BL “inlay” grafting places the donor tissue in a nonanatomical position, which may be inferior to a more natural, subepithelial location.31 Consequently, motivation to refine and update the “inlay” technique to make BL grafting easier while also reducing the risk of intraoperative complications, has resulted in the recent development of BL “onlay” grafting. In this version of the operation, the recipient corneal epithelium is debrided, and an isolated BL graft is simply positioned onto the anterior corneal stroma of the recipient eye and allowed to “dry in.” This drying may “stick” the BL graft onto the surface of the recipient cornea, allowing it to be fixated without sutures or glue. Immediately postoperatively, a bandage CTL may be applied to prevent the onlay graft from being dislodged; after 1 week, the graft may be completely reepithelialized, and the CTL removed.31

The first described case was by Parker et al in 2020,32 in which BL onlay grafting was used to reduce fluctuations in visual acuity after previous radial keratotomy (RK). The patient was a 66-year-old copyeditor with high visual demands and complaints of diurnal visual fluctuation, secondary to corneal instability stemming from numerous RK incisions. BL onlay grafting was performed, and the patient was followed for 12 months postoperatively. After surgery, the patient's subjective complaints of visual fluctuation were reduced from 10 to 3 on a scale of 1 to 10. Best spectacle-corrected visual acuity remained unchanged, although overall, the shape of the cornea showed an overall regularization, with 5.9 D of central steepening in the previously flattest area. This suggests that BL onlay grafting may have the potential to manage patients with subjective complaints of visual fluctuation in eyes with corneal instability secondary to RK.

The second case report describing BL onlay grafting was published by Dapena et al, also in 2020.33 Two eyes with anterior stromal scarring from prior herpetic keratitis underwent isolated BL onlay grafting, in which the epithelium was debrided, a limited superficial keratectomy was performed, and the BL grafts were laid atop the corneal surface and allowed to dry into place. After which, a sheet of amniotic membrane was applied, followed by a soft contact lens. Postoperatively, both eyes showed rapid and complete integration of the BL graft, a significant reduction in anterior stromal scarring and improvement in visual acuity. No evidence of herpetic reactivation, allograft reaction, or graft rejection was observed, with follow-up evaluations of 18 and 12 months for the two operated eyes. These results compliment the first report of BL inlay grafting for the treatment of post-PRK haze and demonstrate that the graft may be effectively fixated on the corneal surface with air-drying alone.

Finally, preliminary use of BL onlay grafting for the treatment of KC has been explored by Dapena et al.34 The early data from 5 eyes shows similar results to its inlay predecessor: approximately 6 D of central corneal flattening and modest improvement in best spectacle corrected visual acuity. Additionally, eyes with anterior stromal scarring can undergo superficial keratectomy during this procedure, which may improve postoperative visual outcomes.


BL grafting emerged from the recognition that both PK and DALK entail significant risks related to the large surface incisions required, bulky donor material, and abundance of sutures involved. Compared to these operations, BL transplantation may represent a less invasive—and therefore potentially safer—alternative to stabilize and normalize the corneal shape, while reducing or even eliminating allograft reaction and graft rejection. In addition, reestablishing a normal BL may also permit a restoration of normal corneal clarity in eyes with anterior scarring secondary to aberrant communication between the epithelial and anterior stromal layers. As a result, BL implantation may have a future role in a large number of anterior corneal pathologies, particularly if onlay grafting can be further demonstrated as successful. Nevertheless, as the studies presented in this review are case reports and small case series, larger randomized studies with longer follow-ups are warranted to further investigate this procedure.


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Bowman layer; corneal transplant; keratoconus; surgical technique

Copyright © 2020 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.