Reis–Bücklers corneal dystrophy (RBCD) is a bilateral and autosomal dominant disease caused by a mutation in keratoepithilin, i.e., BIGH3, also known as transforming human growth factor (TGFBI), on chromosome 5q. This presents early in childhood or teenage years with recurrent painful erosions [4]. In the more advanced form of the disease, corneal opacities form in a geographic pattern leading to a reduction in visual acuity. Visual acuity is also reduced due to acquired astigmatism secondary to corneal irregularity from scarring following multiple recurrent erosions and interestingly, near vision is relatively unaffected compared to distance vision [4].

The histopathological examination of corneas with RBCD reveals abnormal fibrocellular connective tissue replacing Bowman’s layer and growing anterior to it, forming intraepithelial projections, which, together with the surrounding scar tissue (Figure S1), create the biomicroscopic clinical appearances described above [5,6].

PTK has been used as an attempt to improve the vision in Reis–Bücklers corneal dystrophy in various studies. In this method, 193 nm ultraviolet light is used to ablate approximately 0.25 µm of corneal tissue [7]. PTK is less invasive than corneal transplantation, does not carry the risk of rejection, and can be repeated in cases of recurrence [8].

PTK improves the symptoms of recurrent erosions by debriding the irregularities and enhancing visual acuity by ablating the stromal opacity and removing corneal irregularities, thereby reducing astigmatism [7]. In cases of uniform anterior stromal opacities, they can be directly removed with the excimer laser, with the ablation continuing deeper into the stroma thereafter. In patients with significantly uneven epithelium, the ablation is performed following manual removal of the epithelium [7]. In cases of deep ablation, i.e., more than 50 µm of stroma, where a hyperopic shift is not desired, this can be counteracted by concomitant antihyperopic ablation [9,10].

An additional benefit of PTK is the ability to apply refractive correction (photorefractive keratectomy or PRK) in addition to removing the corneal deposits secondary to the corneal dystrophy [7].

Several authors have reported good visual and safe results from PTK in patients with Reis–Bücklers; however, the total numbers of treated cases were low [10,11,12,13,14,15]. Stark and colleagues reported visual improvement and recurrence at 2 years on two eyes with RBCD [10]. McDonnell and Seiler performed PTK on two patients with RBCD through the intact epithelium and achieved visual improvement and decreased symptoms of recurrent erosions [11].

Hahn et al. reported visual improvement at 9 months after PTK in one patient with RBCD whose eyes were both treated with no significant complications and no recurrence to date [12].

Lawless and colleagues treated nine eyes with RBCD with PTK, two of which previously had penetrating keratoplasty (PK) for the same indication. All patients achieved significant visual improvement and recurrent erosion symptoms resolved in all cases postoperatively. However, there were insufficient data on follow-up duration in this study [13].

El Aouni and colleagues treated 10 eyes with RBCD with PTK and achieved visual improvement for up to 1 year postoperatively [14]. Similarly, Kasetsuwan and colleagues reported four cases of successful PTK treatment in Reis–Bücklers dystrophy. The mean follow-up time was 9.9 months (range 6–18 months). Uncorrected visual acuity postoperatively improved in 88.2% of eyes, and ocular discomfort improved in 94.1% of eyes [15].

The above case series demonstrate examples of different stages of the disease being successfully treated with PTK. However, the overall numbers are small, and no guidelines or protocols exist to determine the patient’s suitability and prognosis based on how advanced the disease is, bearing in mind the required depth of ablation.

Pratik and colleagues described a case whereby a high ablation depth PTK was used to treat advanced RBCD where the patient had a thick opacity involving the epithelium, Bowman’s layer and anterior stroma that was 158 μm and 144 μm thick in the right and left eye, respectively. The authors performed a transepithelial ablation of the cumulative depth of 150 μm and 140 μm in the right and left eye, respectively. At 1 month, postoperatively, the patient’s corrected vision improved to 20/30 in both eyes, which was maintained at the 6-month follow-up [8]. This implies that it is feasible to successfully use PTK in advanced Reis–Bücklers’ corneal dystrophy.

Vinciguerra and colleagues showed a variation of a technique of sequential customised therapeutic keratectomy, which achieved a significant visual improvement in their cases from an average VA of 20/50 preoperatively to post-op average VA of 20/25 (p < 0.01) [16]. They showed a significant reduction in the coma aberration and no change in the spherical and trefoil as well as total higher-order aberrations. None of the patients required a corneal graft at approximately 9 months afterwards. Post-operative hyperopia of approximately 1D was common, in line with other authors.

The reported rate of sight-threatening complications post PTK in patients with RBCD is very low. Delayed epithelialisation, corneal scarring, residual corneal opacity, irregular astigmatism and monocular diplopia are uncommonly reported after PTK in eyes with RBCD [10,15].

The main disadvantage of PTK is post-op hyperopia up to 2D in around 80%, described by several authors from the beginning of PTK treatment until this date [4,8,11,14,15].

Oblique angle of the laser beam in the peripheral cornea (and hence decreased peripheral ablation), greater central corneal ablation in cases of deeper corneal pathology, and epithelial hyperplasia at the edge of the ablation zone may contribute to the significant hyperopia post-PTK [10,17].

According to the current literature, the disease recurrence after PTK is high [7,9,18]. Dinh and colleagues reported a recurrence rate of 37%, mostly occurring 12 months post-operatively in the 17 cases of RBCD treated with PTK, and an average recurrence time of 21.6 months post-PTK [9].

Some authors have postulated that mitomycin C (MMC) as an adjunct to PTK is effective in reducing the rate of recurrence and likelihood of dystrophy recurrence [19,20].

Ayres et al. treated two eyes with Reis–Bücklers corneal dystrophy with PTK augmented with MMC; one had recurrence at the margin of the treated area. Miller et al. reported a 73-year-old woman with visually significant Reis–Bücklers dystrophy who underwent PTK of her right eye with 0.02% adjunctive MMC for visual rehabilitation [19]. The left eye had previously undergone PTK on two occasions without MMC, and the dystrophy had recurred following each treatment. One year after the procedure, her MMC-treated cornea remained clear with no recurrence of Reis–Bücklers dystrophy. In Pratik and colleagues’ report, early asymptomatic recurrence was noted at 4 years after augmented PTK, which is a fairly long recurrence-free time [8].

Since these are only case reports or case series without any comparative studies, no definite conclusion about the added benefit of MMC can be drawn. In addition, it is worth highlighting that the early reports of PTK in Reis–Bücklers dystrophy may have included Thiel–Behnke cases, as no additional diagnostic tool, such as genetic testing, was available apart from the clinical assessment to confirm the diagnosis [12,21].

Another strategy to enhance visual outcomes and reduce recurrence rates was described by Vinciguerra and colleagues [16], who reported good outcomes from sequential customised therapeutic keratectomy in 14 eyes of eight patients with RBCD with a mean follow-up of approximately 5 years. The surgical technique involved peeling the epithelium and the subepithelial membrane in patients with RBCD with a surgical spatula and subsequent multiple customised sequential keratectomies with repeated excimer laser photoablations guided by multiple intraoperative topographies to target irregularities. The authors reported a fantastic disease recurrence rate of 14.28% (two eyes) after 5–6 years, which was managed by re-treatment with the same protocol.

Although PTK is currently the most commonly performed treatment for RBCD with a rapid visual improvement, as evident from the above, the literature evidence on the recommended treatment for RBCD is scarce and composed of case reports and case series only with no comparative trials, similar to the rest of the stromal/Bowman layer dystrophies.

The traditional approach to treating visually significant opacities secondary to anterior stromal dystrophies has been with keratoplasty, penetrating or anterior lamellar; however, the literature evidence on the recurrence and success rates, as well as visual outcomes, is scarce. Deep anterior lamellar keratoplasty (DALK) has the advantage of retaining the patient’s own endothelium and, therefore, reducing the risk of endothelial rejection and graft failure [22]. Nonetheless, the reported unaided visual outcomes after keratoplasty for RBCD are not comparable with those of PTK, due to irregular astigmatism [23]. The literature on the recurrence rate of RBCD after penetrating keratoplasty (PK) is very limited. Cadwell reported clinically significant recurrence in the graft 15 years post-op [24].

Another treatment modality that has been described is superficial keratectomy. Wood and colleagues reported treating three patients with this intervention, whereby fibrous corneal tissue was manually dissected. The advantages of the technique are its simplicity and benefit in improving the pain from recurrent erosions; however, the visual improvement post-operatively is modest [25].

Fogla and Knyazer described a variation of the lamellar keratoplasty technique resulting in good visual outcomes in patients with RBCD without the added endothelial rejection risk of a PK [26]. This group reported a microkeratome-assisted two-stage technique of superficial anterior lamellar keratoplasty (SALK) performed in four eyes of two patients with RBCD whereby a 9 mm, 140 μm thick corneal flap was created with a microkeratome in stage one. After 4 weeks, a 7.0 mm central trephination with a depth of 150 μm was performed within the pre-created flap using a Hessberg-Baron suction trephine. Subsequently, donor lamellar tissue was used to replace the host corneal defect in the flap without the need to suture. At an average 19 months postoperatively, there was no recurrence or graft rejection, and the best corrected visual acuity was 20/30 in both eyes. There was no statement on graft dehiscence or dislocation in their report [26].

In summary, due to the anterior location of the deposits, keratoplasty has rarely been used to treat RBCD. Hence, the literature on their outcome is very scarce.