From the University of Heidelberg, Department of Ophthalmology, International Vision Correction Research Centre (IVCRC), Heidelberg, Germany.
This study was supported by a research grant to Drs Holzer and Auffarth by Technolas Perfect Vision GmbH, Munich, Germany. The remaining authors have no financial or proprietary interest in the materials presented herein.
Study concept and design (M.P.H., A.M., A.E., G.U.A.); data collection (M.P.H., A.M., A.E., G.U.A.); interpretation and analysis of data (M.P.H., A.M., A.E., G.U.A.); drafting of the manuscript (M.P.H.); critical revision of the manuscript (M.P.H., A.M., A.E., G.U.A.); statistical expertise (M.P.H., A.M., A.E., G.U.A.); obtained funding (M.P.H., G.U.A.); supervision (M.P.H., G.U.A.)
Correspondence: Mike P. Holzer, MD, University of Heidelberg, Dept of Ophthalmology, International Vision Correction Research Centre (IVCRC), Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Fax: 49 6221 56 8229; E-mail: firstname.lastname@example.org
Since 1949, refractive surgery has been evolving at a fast pace with the development of different techniques from Jose Ignacio Barraquer’s myopic keratomileusis to customized ablations.1–4 Among the available refractive surgery procedures, LASIK is currently the most popular for the correction of myopia and hyperopia, with or without astigmatism.5,6 The final frontier of refractive surgery, however, is the correction of presbyopia and the restoration of accommodation. These aging processes affect each individual beginning near the age of 40 with a complete loss of accommodation by age 50 to 55 years.
To date, treatment of presbyopia consists mainly in the prescription of reading glasses or contact lenses. Surgical attempts to treat presbyopia include removal of the crystalline lens and implantation of a multifocal or accommodative intraocular lens (IOL), intracorneal pin-hole inlays, multifocal excimer laser corneal ablations, and scleral implants.7,8 However, all of these procedures are invasive, and patients are demanding a quick and safe procedure to correct their presbyopia.
With the introduction of femtosecond laser technology in the field of corneal surgery, interest was stimulated in correcting refractive errors by applying femtosecond laser pulses to the corneal stroma without the need of cutting flaps or any other corneal incisions. Several experimental studies have been conducted over the past years.9–17 In October 2007, the first treatments of presbyopia using the TECHNOLAS femtosecond laser (Technolas Perfect Vision GmbH, Munich, Germany) were performed by Luis Ruiz, MD, in Bogotá, Colombia. In 2008, he presented his initial results of a procedure that changes the biomechanical forces of the cornea leading to a multifocal cornea.18 Subsequently, a prospective, ethics committee–approved study was initiated to further validate his findings with the INTRACOR procedure. This study reports the early outcomes of a cohort of presbyopic patients treated with INTRACOR.
Patients and Methods
Twenty-five eyes of 25 patients were enrolled in this prospective clinical study. The study protocol was approved by the Ethics Committee of the University of Heidelberg, Germany. All patients were informed about the study and gave written informed consent prior to enrollment. The inclusion criteria for the study were presbyopia with a minimum near add of +2.00 diopters (D) at 40-cm distance, hyperopia between 0.50 and 1.25 D, cylinder of ≤0.50 D, no prior ocular surgery or any ocular pathology, corrected distance visual acuity (CDVA) of at least 20/25, and corneal thickness of at least 500 μm (thinnest point).
Pupil size under scotopic (0.04 lux), mesopic low (0.4 lux), and mesopic high (4 lux) conditions were measured with the Procyon pupillometer (P2000D; Procyon Instruments Ltd, London, United Kingdom) and patients with >6.5-mm pupil size under scotopic conditions were excluded from the study.
Examinations were performed preoperatively as well as 1 day, 1 week, and 1 and 3 months postoperatively.
Study parameters included uncorrected distance visual acuity (UDVA), CDVA, uncorrected near visual acuity (UNVA), distance corrected near visual acuity, and corrected near visual acuity (CNVA). All near reading tests were performed at a fixed distance of 40 cm from the treated eye using the Sloan ETDRS near charts (Precision Vision, La Salle, Ill). Additionally, detailed slit-lamp examinations including digital photographs as well as corneal topography using Pentacam HR (Oculus Optikgeräte GmbH, Wetzlar, Germany) and endothelial cell count using the Tomey EM 1000 (Tomey GmbH, Erlangen, Germany) were performed.
The preoperative examination was performed within 30 days before INTRACOR treatment. All patients were treated in their non-dominant eye with the TECHNOLAS femtosecond laser using a pachymetry-, age-, and keratometry-reading–adjusted nomogram.
On the day of surgery, the eyes were anesthetized using oxybuprocaine hydrochloride 0.4% eye drops, and under the surgical microscope the line of sight was marked monocularly using the first Purkinje image of a red target light, on which the patient was asked to fixate for the laser treatment. After this centering, the eye was connected to the femtosecond laser using the TECHNOLAS specific curved patient interface device and five purely intrastromal consecutive rings around the line of sight were cut with the laser beam. The depth of these cuts as well as the energy used and spacing follows a proprietary nomogram that includes keratometry and pachymetry data. The treatment time was approximately 20 seconds. Postoperatively, patients received dexamethasone 1% eye drops five times a day and artificial tears as needed and the eyes were covered with a patch for the first few hours. Before leaving the clinic, all patients were examined at the slit lamp where the corneal rings showed dilation due to cavitation gas that typically occurs during femtosecond laser treatment (Fig 1). On the following day, the gas had escaped in all eyes and only fine circular lines were noted in the stroma (see Fig 1).
Figure 1. Slit-Lamp Findings of the Same Eye A) Preoperatively, B) 1 Hour Postoperatively, and C) 1 Day Postoperatively. The Ring Cuts Are Dilated 1 Hour Postoperatively Due to Cavitation Gas that Escapes During the First Few Postoperative Hours.
For statistical calculations, data were analyzed using Winstat Add-in for Microsoft Excel (R. Fitch Software, Bad Krozingen, Germany). The level of significance was set at P=.05 and the Friedman test was used.
Mean age of the 25 patients who underwent the INTRACOR procedure was 56.2±5.79 years (range: 47 to 67 years). Mean preoperative distance spherical equivalent refraction was +0.60±0.26 D with a mean sphere of +0.75±0.23 D and a mean cylinder of −0.33±0.17 D. Corrected distance visual acuity was 0.11±0.11 logMAR (20/25 Snellen) and UNVA tested with Sloan ETDRS near charts at 40-cm distance was 0.7±0.16 logMAR. Mean UNVA improved on postoperative day 1 to 0.39±0.25 logMAR whereas the mean UDVA was 0.09±0.10 logMAR. Steroid eye drops were discontinued after 1 week. Visual acuity remained stable over the follow-up period of 3 months with a mean UNVA of 0.26±0.21 logMAR (Fig 2) and mean UDVA of 0.05±0.1 logMAR (20/23 Snellen). Detailed visual acuity outcomes are shown in Tables 1 and 2.
Figure 2. Development of Mean Uncorrected near Visual Acuity (UCNVA) (logMAR) During the 3-Month Follow-Up Period. The Gain of Visual Acuity Was Statistically Significant (P<.01, Friedman Test).
Table 1: Mean Visual Acuity of 25 Eyes Treated with INTRACOR
Table 2: Individual near and Distance Visual Acuity Outcomes for 25 Patients Treated with INTRACOR
The mean gain of UNVA lines was 4.42 (from preoperatively 6.96±0.66 lines to 11.38±0.91 lines 3 months postoperatively) with a range from no line (n=1) up to nine lines (n=1) of gain. Maximum loss of CDVA 3 months postoperatively was two lines in two eyes whereas three eyes gained one line of CDVA (Fig 3). The mean loss of CDVA was −0.46±0.83 lines. At that time, the mean sphere for distance was 0.15±0.31 D and mean cylinder was −0.42±0.23 D. In some patients, corneal topography showed a steepening of the central cornea (Fig 4), and the mean anterior corneal asphericity at 6.0 mm changed from −0.20±0.16 to −0.26±0.18 whereas the posterior asphericity changed from −0.34±0.16 to −0.41±0.18.
Figure 3. Lines of Corrected Distance Visual Acuity (CDVA) Gained and Lost at 3 Months Postoperatively. Two Eyes Lost Two Lines of CDVA Whereas Three Eyes Gained One Line of CDVA.
Figure 4. Example of Corneal Anterior Surface Changes Leading to a Steeper Central Cornea (pentacam). Lower Left) Preoperative Anterior Dioptric Power, lower Center) 3-Month Postoperative Dioptric Power, lower Right) Difference Map of Dioptric Power.
Endothelial cell measurements showed a stable mean cell count over 3 months with 2502 cells/mm2 preoperatively and 2472 cells/mm2 3 months postoperatively. Corneal pachymetry showed no change of thinnest point before and after surgery (544.86±26.37 μm vs 545.50±23.81 μm).
The correction of presbyopia is an important field of refractive surgery with increasing demands for safe and effective surgical procedures.4 Early steps in presbyopia surgical treatment have been monovision procedures.19 Intraocular procedures are refractive lens exchange and implantation of multifocal or accommodative IOLs.4,7,8 Corneal procedures include excimer laser treatments either as monovision procedures or as multifocal corneal ablations and conductive keratoplasty.19–21 The good performance of excimer laser treatments for refractive errors other than presbyopia has been shown and proven during the past two decades, and treatments for presbyopia using multifocal ablations have been tested in the past few years with satisfying outcomes.22–25
The safe and precise application of femtosecond laser cuts has been demonstrated in multiple studies.25–29 Early studies evaluating intrastromal effects of pico- and femtosecond laser treatments of corneal tissue started more than 15 years ago.9–15 With improvement of the technology, new attempts were initiated using femtosecond lasers. Meltendorf et al16 were able to demonstrate a favorable corneal wound-healing response preserving corneal transparency, concluding that femtosecond lasers can be used to treat refractive errors. These results were the beginning for the use of such intrastromal corrections in human eyes. The first patients were treated by Ruiz.18 Other femtosecond laser approaches focus on treatments of the crystalline lens to regain lenticular elasticity.30 Because the lens shows a change of elasticity over time, this approach might need several treatments as time passes.
The results of our prospective clinical study confirm the findings presented by Ruiz.18 All patients were only treated in their non-dominant eye and the majority gained several lines of near visual acuity. Some of the eyes showed only slight improvement in near visual acuity, which requires further investigation. The parameters tested thus far do not indicate any specific factors, such as preoperative keratometry or corneal thickness, which might have lowered the outcomes. Also, the centering of the rings did not correlate with the outcomes in this cohort of patients and a larger group of patients may be needed to detect correlations in this matter. More than likely, the interaction of laser energy applied and corneal elasticity and refractive power of these patients was not optimal. A retreatment, however, was not possible at this stage of the study due to the strict study protocol. However, 54.2% of patients treated achieved at least 20/25 distance visual acuity and were also able to read newsprint (equal to Jaeger 3).
The side effects seen to date are minimal with a slight disturbance of visual acuity during the early postoperative hours due to the cavitation gas bubbles located in the cornea. These resolve over the following hours, and on the first postoperative day, most patients achieve good distance and near visual acuity. The two-line loss of CDVA in 8.3% of patients 3 months postoperatively will need further investigation during the next follow-up examinations. However, none of the patients lost more than two lines of CDVA. Rigid contact lenses should be fitted at 12-month follow-up to determine whether the distance visual acuity can be further improved or if the changes that occur at the posterior surface of the cornea also lead to a decrease in distance visual acuity in these patients. These findings together with 1-year results, including quality of life questionnaire outcomes, will be published at a later date. Wavefront measurements and dynamic stimulation of accommodation (DSA) should be a helpful tool in this regard.
Corneal biomechanics seem not to be affected as per initial reports from Ruiz. However, current technology might not be capable of measuring slight biomechanical changes occurring in the central part of the cornea. None of the patients experienced any postoperative infection or inflammation, but a prophylactic anti-inflammatory treatment with unpreserved topical steroids was administered for the first week. The minimal to no risk of corneal infections following the INTRACOR procedure due to the remaining integrity of the corneal surface is an advantage over many other surgical procedures to treat presbyopia. This seems to be especially advantageous in patients who do not have any higher refractive distance errors. The presbyopic age group might have a slightly increased risk for infections following intraocular surgeries, and the risk of endophthalmitis following cataract surgery and especially following refractive lens exchange is still a fear for many patients and surgeons. Semoun et al31 reported the first case of bacterial keratitis after presbyopic LASIK and emphasized that patients need to be informed in detail about this potential sight-threatening risk prior to presbyopic excimer laser surgery.
The biomechanical changes that occur following the INTRACOR procedure require further investigation and current technologies, eg, corneal topography, often cannot detect the minimal changes that occur at the anterior and posterior surface of the cornea. In our study, some patients showed corneal refractive changes with steepening of the central cornea; however, these did not always correlate with the visual acuity of the patient.
The laser-induced biomechanical response of the cornea, which subsequently leads to the beneficial refractive effect on visual acuity, mostly manifests itself within some minutes up to a few hours following surgery and shows a high stability towards longer observation periods. Our initial results of the INTRACOR procedure are promising and stimulating for further research on femtosecond laser treatment of other refractive errors such as myopia, hyperopia, and astigmatism. Further examinations such as reading speed, wavefront measurements, contrast sensitivity, and quality of life questionnaires are currently being performed with this cohort of patients to evaluate the mid- and long-term stability of this new corneal intrastromal procedure.
- Pallikaris IG, Papatzanaki ME, Stathi EZ, Frenschock O, Georgiadis A. Laser in situ keratomileusis. Lasers Surg Med. 1990;10:463–468. doi:10.1002/lsm.1900100511 [CrossRef]
- Seiler T. Current evaluation of myopia correction with the excimer laser [German]. Ophthalmologe. 1995;92:379–384.
- Barraquer JI. The history and evolution of keratomileusis. Int Ophthalmol Clin. 1996;36:1–7. doi:10.1097/00004397-199603640-00003 [CrossRef]
- Holzer MP, Rabsilber TM, Auffarth GU. Presbyopia correction using intraocular lenses [German]. Ophthalmologe. 2006;103:661–666. doi:10.1007/s00347-006-1382-z [CrossRef]
- Solomon KD, Holzer MP, Sandoval HP, Vargas LG, Werner L, Vroman DT, Kasper TJ, Apple DJ. Refractive Surgery Survey 2001. J Cataract Refract Surg. 2002;28:346–355. doi:10.1016/S0886-3350(01)01318-9 [CrossRef]
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- Auffarth GU, Rabsilber TM, Kohnen T, Holzer MP. Design and optical principles of multifocal lenses [German]. Ophthalmologe. 2008;105:522–526. doi:10.1007/s00347-008-1744-9 [CrossRef]
- Pepose JS, Qazi MA, Davies J, Doane JF, Loden JC, Sivalingham V, Mahmoud AM. Visual performance of patients with bilateral vs combination Crystalens, ReZoom, and ReSTOR intraocular lens implants. Am J Ophthalmol. 2007;144:593–594. doi:10.1016/j.ajo.2007.05.036 [CrossRef]
- Vogel A, Capon MR, Asiyo-Vogel MN, Birngruber R. Intraocular photodisruption with picosecond and nanosecond laser pulses: tissue effects in cornea, lens, and retina. Invest Ophthalmol Vis Sci. 1994;35:3032–3044.
- Juhasz T, Hu XH, Turi L, Bor Z. Dynamics of shock waves and cavitation bubbles generated by picosecond laser pulses in corneal tissue and water. Lasers Surg Med. 1994;15:91–98. doi:10.1002/lsm.1900150112 [CrossRef]
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- Vogel A, Günther T, Asiyo-Vogel M, Birngruber R. Factors determining the refractive effects of intrastromal photorefractive keratectomy with the picosecond laser. J Cataract Refract Surg. 1997;23:1301–1310.
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- Lubatschowski H, Maatz G, Heisterkamp A, Hetzel U, Drommer W, Welling H, Ertmer W. Application of ultrashort laser pulses for intrastromal refractive surgery. Graefes Arch Clin Exp Ophthalmol. 2000;238:33–39. doi:10.1007/s004170050006 [CrossRef]
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- Ruiz LA. Hawaiian Eye Foundation’s International Award for Excellence. Presented at: Hawaiian Eye Meeting. ; January 23, 2008. ; Kona, Hawaii. .
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- Pinelli R, Ortiz D, Simonetto A, Bacchi C, Sala E, Alió JL. Correction of presbyopia in hyperopia with a center-distance, paracentral-near technique using the Technolas 217z platform. J Refract Surg. 2008;24:494–500.
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- Holzer MP, Rabsilber TM, Auffarth GU. Femtosecond laser-assisted corneal flap cuts: morphology, accuracy and histopathology. Invest Ophthalmol Vis Sci. 2006;47:2828–2831. doi:10.1167/iovs.05-1123 [CrossRef]
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- Semoun O, Bourcier T, Dupas B, Puech M, Maftouhi AE, Borderie V, Laroche L. Early bacterial keratitis after presbyopic LASIK. Cornea. 2008;27:114–116. doi:10.1097/ICO.0b013e318157a12d [CrossRef]
Mean Visual Acuity of 25 Eyes Treated with INTRACOR
|Visual Acuity||Mean± Standard Deviation (logMAR)|
|Preoperative||Day 1||Week 1||Month 1||Month 3|
Individual near and Distance Visual Acuity Outcomes for 25 Patients Treated with INTRACOR
|Patient||UDVA logMAR||UNVA logMAR||CDVA logMAR|
|Preop||3 mos Postop||Lines Gained (+) or Lost (−)||Preop||3 mos Postop||Lines Gained (+)||Preop||3 mos Postop||Lines Gained (+) or Lost (−)|