Real-world Comparison of StreamLightTM trans-PRK and Conventional PRK With Regard to Refractive Outcome, Wound Healing, Pain Intensity and Visual Recovery Time

Purpose To compare clinical outcomes of single-step transepithelial photorefractive keratectomy (tPRK) and conventional photorefractive keratectomy (PRK) regarding refractive outcome, visual acuity, wound healing, pain intensity and visual recovery time. In this prospective clinical observational study 200 eyes of 100 consecutive patients with mild to moderate myopia with or without mild astigmatism were included. One hundred eyes each were treated with StreamLight TM tPRK or conventional PRK with the WaveLight ® EX500 excimer laser. Visual acuity (Decimal) was assessed preoperatively and at day 4, 7 and 6 weeks postoperatively. Wound healing (hours between surgery and complete epithelial closure) was monitored at the slit lamp. Subjective pain intensity level was evaluated by a numeric pain rating scale (0 – 15) at day 4.


Introduction
The introduction of single-step transepithelial photorefractive keratectomy (tPRK) procedures in recent years has led to a renaissance of surface ablation treatments in refractive surgery. Since decades, photorefractive keratectomy (PRK) is a well-established and safe surface ablation technique to correct low to moderate myopia and astigmatism [1,2]. Moreover, it is also suitable for patients who reject or are not eligible for laser in situ keratomileusis (LASIK), e.g. due to thin corneas or subtle topographic irregularities [3,4]. Refractive outcomes after PRK are good and complications like corneal haze are rare [5,6]. However, a long visual rehabilitation period and considerable postoperative pain deter many patients from opting for PRK [7,8]. Since a few years "no-touch" single-step tPRK procedures are available from various manufacturers and have proven to be effective and safe [9 -10 ]. StreamLight™ is a novel, one-step tPRK procedure in which the epithelium is rst removed by phototherapeutic keratectomy (PTK) immediately followed by PRK in a single procedure using the Wavelight EX500 excimer laser. Due to newly calculated nomograms, size and location of the PTK treatment zone are automatically aligned with the PRK ablation pro le and centration is only required once in StreamLight TM procedure. Moreover, a multidimensional eye tracker is active throughout the complete procedure.
The purpose of our prospective observational study was to evaluate the clinical outcomes of StreamLight TM tPRK in daily clinical practice and compare them to those of conventional PRK regarding refractive outcome, visual acuity, wound healing, pain intensity and visual recovery time.

Study design and patients
This is a prospective clinical observational study including 200 eyes of 100 consecutive patients with mild to moderate myopia (-2.0 D to -6.0 D spherical equivalent) and mild (0.0 D to -2.5 D) astigmatism who underwent conventional PRK or tPRK at the Augenlaserzentrum Neu-Ulm, Germany between January and December 2019. After comprehensive information about risks and bene ts of the two surgical techniques, patients were free to choose one of the two procedures. All patients provided a signed informed consent form for data collection, evaluation and publication. The research has been carried in accordance with the Declaration of Helsinki. All methods were performed in accordance with the relevant guidelines and regulations, although ethical approval was not required and deemed unnecessary according to national regulations of the Bavarian Medical Association (Bayerische Landesärztekammer (BLÄK) Ethikomission (ethics committee), Mühlbaurstraße 16, 81677 München), which states that study projects with anonymized data are not subject to consultation. All patients provided a signed informed consent form for data collection and consent to participate in this study with data evaluation and publication.
All patients quali ed for surface ablation according to the German standards for surface ablation of the German Committee of Refractive Surgery (Kommission Refraktive Chirurgie) [12].
Exclusion criteria were unstable refraction, severe ocular surface disease, corneal epithelial pathology, keratoconus, any posterior segment pathology or any previous intraocular or corneal surgery. All patients were advised to discontinue contact lens wear for a minimum of 3 weeks prior to preoperative examination and treatment.
Pre-and postoperative assessments Preoperatively, all patients underwent a complete eye examination including uncorrected distance visual acuity (UCDVA) and best corrected distance visual acuity (BCDVA) assessment, manifest refraction, autokeratometry, intraocular pressure measurement, and slit lamp examination to evaluate the anterior segment and the fundus. Visual acuity (at 5 m, decimal) and manifest refraction measurements as well as corneal topography assessment by Allegro Topolyzer-Vario (WaveLight, Erlangen, Germany) and Scheimp ug tomography examination by Allegro Oculyzer ІІ (WaveLight, Erlangen, Germany) were performed by one experienced optometrist.

Surgical procedures
All surgical procedures were performed bilaterally at the same day, with the right eye being treated rst by one single surgeon (HCG). The wavefront-optimized (WFO) ablation pro le was planned using the standard planning software including WaveLight nomograms and was based on manifest refraction. In StreamLight TM procedures, a newly calculated shot matrix enables an equal ablation of the epithelium over the treatment zone (7mm for myopia and 9 mm for mixed myopic astigmatism).
In both groups standard wavefront optimization laser ablation pro les with a refractive ablation zone of 6.5 mm in all cases were applied and the use of Mitomycin C was avoided according to the recommendations of the German Committee of Refractive Surgery [12].
The standard preoperative procedure for both procedures was the same. Topical proparacaine hydrochloride 0.5% (Alcaine; Alcon Laboratories, Inc., Fort Worth, TX, USA) eye drops were instilled twice directly before surgery. In the PRK group, de-epithelialization was performed with a 9 mm rotating brush (Amoils Rotary Epithelial Scrubber, Innovative Excimer Solutions, Inc., Toronto, Canada) and remaining epithelial cells were removed using a dry PVA eye spear. Subsequently, PRK laser ablation was carried out followed by 1 minute of corneal and conjunctival cooling with ice-cold BSS administered with a syringe. In the tPRK group, conjunctiva and cornea were pre-cooled with ice-cold BSS from a syringe for 30 seconds. After removing excessive liquid from the conjunctiva and cornea with a dry PVA eye spear, deepithelialization was performed using the StreamLight TM PTK mode for 22 -30 seconds depending on preexisting astigmatism. StreamLight TM allows to individually determine the epithelial ablation depth between 45 µm and 65 µm after epithelial mapping. In our daily practice we usually work with an epithelial ablation depth of 55 µm. After the PTK mode, the cornea was checked and any remaining epithelial cells were removed mechanically with a dry PVA eye spear. After an interruption of around 10 seconds to cool down the cornea, PRK laser ablation was applied followed by 1-minute cooling of the cornea and conjunctiva with ice-cold BSS administered with a syringe. Following both laser procedures preservative-free O oxacin and corticosteroid eye drops were instilled, a pre-cooled soft bandage contact lens (Acuvue ®; Johnson and Johnson Vision Care, Inc., Jacksonville, USA) was placed on the cornea and preservative-free eye drops containing 0,15 % sodium hyaluronate were applied. The soft bandage contact lens was removed 4 days after surgery in both groups. Patients were advised to continue three times daily with preservative-free corticosteroid eye drops for 4 weeks and to regularly use preservativefree 0,15 % sodium hyaluronate eye drops at least 5 times per day.

Statistical analysis
Results are expressed as mean ± standard deviation. Data were analyzed using Statview 5.01 software for Windows (Abacus Concepts, Inc., Berkeley, California). For determining statistical signi cance between both groups, the non-parametric Mann-Whitney U test and the t-Test for independent samples were performed (p < 0.05 considered statistically signi cant).

Results
Demographic and baseline characteristics are displayed in Table 1. There was no statistically signi cant difference regarding demographic and baseline characteristics between the two groups (p > 0.05). Postoperative results are summarized in Table 2. Visual rehabilitation was achieved signi cantly faster in the tPRK group. At days 4 and 7, the mean monocular UCDVA (decimal) was signi cantly better in the tPRK group than in the PRK group (p < 0.001), while six weeks after surgery both groups had achieved a comparable mean UCDVA of better than 1.0 (p > 0.05) (Fig 1). Four days after surgery 72% of eyes in the tPRK group had a UCDVA of 0.7 or more, while no eye in the PRK group reached that level. Up to one week postoperatively, the proportion of eyes with an UCDVA of 0.7 had further increased to 89% in the tPRK group and to 34% in the PRK group. BCDVA was similar in both groups six weeks after surgery and no patient had lost a line of preoperative BCDVA. The levels of accuracy of refractive correction were high, with no statistically signi cant difference between both groups regarding mean spherical equivalent off target at six weeks postoperatively (p > 0.05) (Fig. 2). The achieved SE was within 1.0 D of the intended SE for all treated eyes and within ± 0.5 D for 84% of eyes in the PRK group and within -0.25 D and + 0.5 D for 82% of eyes in the tPRK group. Epithelial wound healing was achieved signi cantly faster in the tPRK group. Complete wound closure was observed in the tPRK group after in mean 45.76 ± 9.46 hours, whereas it took in mean 59.10 ± 6.79 hours in the PRK group (p < 0.0001) (Fig. 3). Maximum pain level within the rst 4 days after surgery revealed signi cantly less pain in the tPRK group compared to the PRK group (p < 0.0001) (Fig 4). No patient developed a postoperative corneal haze during the observation period and no other adverse effects or complications were observed.

Discussion
To the best of my knowledge, this is the rst study to evaluate the clinical results of StreamLight TM tPRK based on Alcon/Wavelight ablation pro le in patients with mild to moderate myopia with and without mild astigmatism compared to conventional PRK. The new StreamLight TM method requires only three parameters to calculate the WFO ablation pro le: manifest refraction, optical zone and epithelial depth. This helps to reduce possible sources of error in the calculation of the ablation pro le, especially in everyday hospital routine, and to implement e cient work ows and a very convenient calculation of the ablation pro le.
The two patient groups examined in our study were comparable in terms of preoperative characteristics and re ect the typical patient population seeking for refractive correction. The key ndings of our study are that both treatments provide safe and effective refractive correction, but StreamLight TM tPRK is superior to conventional PRK in terms of epithelial healing, postoperative pain and visual recovery time.
This considerably increases comfort and may contribute to greater patient satisfaction with tPRK treatment.
The main reason for accelerated epithelial healing and reduced pain in the tPRK group could be the smaller epithelial defect. In conventional PRK the epithelial removal zone is larger than the ablation zone, which might delay re-epithelialisation, whereas in StreamLight TM , the size of the epithelial removal zone matches the size of the ablation zone. This might contribute to a faster re-epithelisation. In addition, also the PTK treated stromal bed can have provided the ideal basis for a fast and rmly adherent reepithelialisation. The shorter epithelial healing time after tPRK observed in our study has been shown in other clinical studies evaluating tPRK treatments performed with other nomograms and other laser systems. Fadlallah et al observed an average period to complete healing of 2.5 days in the tPRK group versus 3.7 days in the conventional PRK group while Naderi et al reported 2.9 days and 3.3 days respectively [11,13]. Although these results were obtained in different studies and therefore cannot be directly compared, it still has to be noted that in our study complete closure of the epithelium after StreamLight TM tPRK was achieved in average after 46 hours, i.e. in less than two days. Another factor that may have contributed to faster wound healing after tPRK is signi cantly less pain. One of the most frequent complications after PRK is pain [14]. However, pain and wound healing are closely related and form a vicious circle: when there is pain, more in ammatory parameters are released through the tear lm and the conjunctiva, which is thought to slow down wound healing. In addition, pain contributes to patients squeezing their eyes more often, which in turn mechanically impairs the newly forming epithelial cell layer. In order to minimize post-operative pain, our conventional PRK procedure includes the avoidance of alcohol for epithelial removal, direct cooling of the cornea after ablation and the use of a bandage contact lens. Nevertheless, StreamLight TM tPRK patients still experienced signi cantly less pain during the early postoperative period compared to PRK patients. In mean, the pain score of tPRK patients was 5.4, only half as high as the PRK patients' pain score of 10.8. This is in line with the results from other clinical studies on tPRK, indicating that postoperative pain after tPRK is lower compared to conventional PRK [10,11,13].
According to our patients, one of the main reasons for their high satisfaction with the Streamlight™ tPRK, in addition to the accelerated wound healing and signi cant pain reduction, was the rapid visual rehabilitation. Although patients in both groups achieve a very good mean UCDVA of over 1.0 after 6 weeks, visual acuity in the tPRK group is signi cantly better from day 4. Almost three-quarters of all tPRK eyes but none of the PRK eyes achieved an UCDVA of 0.7 or better four days postoperatively. For patients, this is a crucial visual threshold, because permission for car driving is only given from a UCDVA of 0.7 in Germany [15]. Moreover, the rapid visual recovery after StreamLight TM tPRK can -combined with clever planning of the procedure close to the weekend -help to ensure that patients only have to take one day off work. Especially for the mostly young, employed patients this is another a very important aspect to choose this procedure.
Our study has limitations that should be addressed. First, the rate of epithelial healing was not objectively assessed by an image analysis software. Secondly, a longer follow-up period is required to fully assess the development of visual acuity and refractive stability. However, the six-week follow-up period chosen in our study allows a proper evaluation visual recovery time, pain sensation and wound healing.
Overall, this study provides important insights from daily clinic routine with this novel tPRK method. Our results show that StreamLight TM tPRK is a safe and effective treatment option for the correction of low to moderate myopia, offering faster visual recovery and epithelial healing compared to conventional PRK, with less pain. It can therefore be considered a good treatment option especially for patients who refuse or are not eligible for Femto-Lasik, but at the same time demand a faster and more comfortable recovery time than conventional PRK can offer. To con rm these results, further prospective, randomized studies with longer follow-ups are required to evaluate the e cacy and safety of this procedure in more detail. All patients provided a signed informed consent form for data collection and consent to participate in this study with data evaluation and publication. The research has been carried out within an appropriate ethical framework in accordance with the Declaration of Helsinki

Consent for publication
Not applicable.

Availability of data and materials
The datasets generatedand/or analyzed during the current study are not publicly available due to institutional policy but are available from the corresponding author on reasonable request.

Competing interests
The author has no nancial or proprietary interest in any material or method mentioned.
Funding: This publication was supported by an independent publication grant # 63482385 from Alcon.

Author contributions
The author, Dr. Harald Gaeckle, was involved in data collection, performed data analysis and wrote the manuscript. The author has read and approved the nal manuscript.