ARTICLE

Evaluation of cornea

l endothelial cell lossand corneal thickness after cataract removal

with light-adjustable intraocular lensimplantation: 12-month follow-upFritz H. Hengerer, MD, H. Burkhard Dick, MD, Simone Buchwald,

Werner W. H€utz, MD, Ina Conrad-Hengerer, MD

Q 2011 A

Published

SCRS an

by Elsev

PURPOSE: To determine quantitative changes in endothelial cell loss and corneal thickness inpatients having cataract surgery and implantation of a light-adjustable intraocular lens (IOL) tocorrect residual postoperative refractive errors by application of a spatially profiled near-ultraviolet (UV) light.

SETTING: Ruhr University Eye Clinic, Bochum, Germany.

DESIGN: Cohort study.

METHODS: The light-adjustable IOLs were implanted after phacoemulsification cataract surgeryand treated with spatial-intensity-profiled UV light at 365 nm to induce a targeted refractivechange. Once the desired correction was achieved, the light-adjustable IOL was treated again tolock-in the lens power. Noncontact computer-assisted endothelial cell microscopy and cornealpachymetry were performed before surgery; after surgery before adjustment; before lock-in; and1, 3, 6, and 12 months after final lock-in.

RESULTS: One hundred twenty-two eyes were evaluated 12 months after lock-in. The meancumulative UV light dose at the cornea was 61.47 J/cm2 G 2.37 (SD). The mean endothelial cellloss was 6.91% G 3.66% 2 weeks after surgery before adjustment and 6.57% G 3.81% 12months after lock-in. The mean relative change in corneal thickness from preoperatively was6.18% G 3.97% 2 weeks postoperatively and �0.64% G 1.88% 12 months after lock-in.

CONCLUSIONS: Endothelial cell loss and corneal thickness change 12 months after lock-in agreedwell with those reported in the literature after phacoemulsification with IOL implantation. The UVlight exposure for adjustment and lock-in procedures did not add to the endothelial damagecaused by the cataract surgery.

Financial Disclosure: No author has a financial or proprietary interest in any material or methodmentioned.

J Cataract Refract Surg 2011; 37:2095–2100 Q 2011 ASCRS and ESCRS

Implantation of a light-adjustable intraocular lens(IOL) (Light-Adjustable Lens, Calhoun Vision, Inc.) of-fers the opportunity to correct postoperative residualrefractive errors in a nonsurgical way with refractivestability over time.1–9 Selective irradiation of theimplanted light-adjustable IOL using a digital light-delivery device (Carl Zeiss Meditec AG) to delivertargeted doses of spatially profiled ultraviolet (UV)light at 365 nm modifies the lens curvature, resultingin a predictable spherical and/or cylindrical powerchange postoperatively. By controlling the

d ESCRS

ier Inc.

irradiation dose and spatial irradiance profile, therefractive power of the light-adjustable IOL can bemodified accordingly to add or subtract sphericalpower and reduce astigmatic errors.

Until now, little has been reported on the potentialrisk for UV light damage to the human ocular surfaceas well as intraocular structures with this emergingtechnology. In terms of UV phototoxicity, the corneaand retina remain the most vulnerable ocular struc-tures. The light-adjustable IOL optic has a siliconelayer of up to 100 mm molded on the posterior surface

0886-3350/$ - see front matter 2095doi:10.1016/j.jcrs.2011.07.026

2096 CORNEAL ENDOTHELIAL CELL LOSS AND THICKNESS WITH LIGHT-ADJUSTABLE IOLS

of the lens, with a higher concentration of UV absorberthan the photoreactive lens bulk material to enhancethe UV light–filtering properties to protect the retina.Alterations in endothelial structures, such as endothe-lial cell loss, may lead to corneal thickening as a resultof cataract surgery and application of UV light dosesduring adjustment and lock-in of the light-adjustableIOL. Previous studies assessed the safety of UV lightuse in animal eyes, and recently Lichtinger at al.10 pub-lished the first clinical results of endothelial cell mea-surements in 10 patients with a follow-up of 6 months.

To determine quantitative changes in endothelialcell count (ECC) and corneal thickness, we performedan observational prospective cohort study of patientshaving cataract surgery with implantation of a light-adjustable IOL followed by postoperative irradiationwith spatially profiled UV light for adjustments andlock-ins.

PATIENTS AND METHODS

This prospective study involved eyes that had a 12-monthfollow-up after lock-in of the light-adjustable IOL. The Ethi-cal Committee, Ruhr University of Bochum, approved thetrial, and all aspects of the Helsinki Declaration were ob-served. All patients enrolled had a visually significant cata-ract, had a dilated pupil width of 7.0 mm or more, andwere willing to volunteer for the trial after providinginformed consent. Exclusion criteria included pathologiesof the cornea (!1500 endothelial cells/mm2), maculardegeneration, glaucoma, history of uveitis, zonular laxity,dehiscence or pseudoexfoliation, and complications duringcataract surgery that may affect postoperative pupil dilationor IOL centration or tilt.

The IOL power was selected based on standard ocularbiometry data (IOLMaster, Carl Zeiss Meditec AG), themanufacturer’s recommended A-constant of 118.0, anda modified standard IOL power calculation formula pro-vided by the manufacturer.11,12

Surgical Technique

All surgeries as well as the adjustments and lock-in proce-dures were performed by the same surgeon (F.H.H.). Thetechnique included local anesthesia and a 2.8 mm clear cor-neal incision. After instillation of sodium hyaluronate 1.0%(Healon) into the anterior chamber to protect the endothe-lium, a well-centered continuous curvilinear anterior

Submitted: April 19, 2011.Final revision submitted: July 23, 2011.Accepted: August 9, 2011.

From the Center for Vision Science (Hengerer, Dick, Buchwald,Conrad-Hengerer), Ruhr University Eye Clinic, Bochum, and theEye Clinic (H€utz), Bad Hersfeld, Germany.

Corresponding author: Fritz H. Hengerer, MD, Center for VisionScience, Ruhr University Eye Hospital, In der Schornau 23 – 25,44892 Bochum, Germany. E-mail: fritz.hengerer@kk-bochum.de.

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capsulorhexis between 4.5 mm and 5.5 mm in diameter wascreated. This was followed by phacoemulsification usingthe stop-and-chop technique. Without enlarging the tunnel,a 3-piece silicone light-adjustable IOL was implanted in thecapsular bag through a single-use push-type injector system(CalhounVision, Inc.). After the ophthalmic viscosurgical de-vicewas carefully removed, the eyewas coveredwithapatch.

Standard topical ofloxacin and dexamethasone eyedropswere administered 4 times daily for the first week, afterwhich the dosage was gradually tapered over 6 weeks. Allpatients were required to wear UV light–filtering photochro-mic spectacles (7EYE, Calhoun Vision) at all times aftercataract surgery until the final lock-in treatment.

Light-Adjustable Intraocular Lens

The light-adjustable IOL is supplied in a range ofC10.0 toC30.0 diopters (D) and C17.0 to C24.0 D in 0.5 D incre-ments. Spherical and cylindrical power adjustments in therange ofG0.25 toG2.00 D can be made by controlled appli-cation of UV light (365 nm). The IOL is implanted in the pos-terior chamber after phacoemulsification lens extractionusing standard surgical techniques. After postoperativerefractive stabilization, typically 10 to 21 days, the patientreturns for an examination and refraction by the surgeonto determine whether adjustment in spherical and/or cylin-drical power is required.

The power is adjusted by irradiating the IOL with a tar-geted dose of profiled UV light delivered using the digitallight-delivery device to produce an individually plannedchange in the power of the implanted IOL. The digitallight-delivery device is designed to produce a predictablepower change in the light-adjustable IOL using a 365 nmwavelength, spatial irradiance profile, and specific diameter.Controlling the irradiation dose (ie, beam irradiance and du-ration) and spatial irradiance profile modifies the refractivepower of the IOL to add or subtract spherical power or toreduce astigmatic error. Intraocular lenses not requiring a re-fractive power adjustment are treated with a power-neutraldose to consume macromers without affecting refraction.During the commencement of light-adjustable IOL irradia-tion, the patient is instructed to fixate on an alignment target.This irradiation treatment exposure is delivered in a continu-ous dose. After irradiation, the adjusted IOL power stabilizeswithin aminimumof 24 hours after adjustment. Amaximumof 3 adjustments were used in some patients in this study toachieve the desired refractive outcome. One day after finaladjustment, the entire IOL can be irradiated to polymerizethe remaining photosensitive macromers and prevent anadditional change in IOL power. This final irradiation proce-dure is referred to as lock-in. For safety reasons, 2 lock-inprocedures are recommended.

Corneal Endothelium

The ECC and corneal thickness were measured preopera-tively; postoperatively before each adjustment (maximum3);before lock-in procedures; and 1, 3, 6, and 12 months after fi-nal lock-in. Preoperatively and postoperatively, all patientshad a full clinical examination including manifest refraction,Snellen corrected distance visual acuity, ECC using anendothelial noncontact specular microscope (Sea Eagle,Rhine-Tec), and Scheimpflug imaging (Pentacam HR,Oculus, Inc.) of the anterior segment including cornealpachymetry, topography, and keratometry.11 The surfaceof the endothelium measured at 970 mm � 720 mm was

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Figure 1. Cumulative UV dose in J/cm2 applied during adjustmentsand lock-ins of the implanted light-adjustable IOLs in 125 eyes. Thebottom and top of the box are the 25th and 75th percentiles, respec-tively, and the band near the center is the 50th percentile (median).The bars outside the box indicate the maximum and minimum ofall data (UV Z ultraviolet).

Figure 2. Cumulative applied UV dose in J/cm2 used for adjust-ments and lock-ins (UV Z ultraviolet).

2097CORNEAL ENDOTHELIAL CELL LOSS AND THICKNESS WITH LIGHT-ADJUSTABLE IOLS

scanned by the endothelial noncontact specular microscope.Fifty images were generated automatically to analyze thecenter of the cornea. An automatic hexagonal cell countwas performed, and the mean values were derived. The per-centage loss in ECC and relative change in central cornealthickness (CCT) were calculated using the following formu-las (where pre Z preoperative; post Z postoperative):

Loss of ECC ð%ÞZECCpre � ECCpost

ECCpre

and

CCT ð%ÞZCCTpost � CCTpre

CCTpre

Statistical Analysis

Figure 3. Number of adjustments applied in 125 eyes.

All descriptive statistical analysis was performed usingSPSS software (version 19.0, SPSS Inc.). The t test was usedto compare the sample means. A P value less than 0.05 wasconsidered statistically significant. Continuous variableswere described with mean G standard deviation (SD),median, minimum, and maximum values. Box plots wereused for analysis of endothelial cell loss and cornealthickness.

RESULTS

The study enrolled 125 eyes (66 right, 69 left) of 83patients (46 women, 37 men). The mean age of thepatients was 70.5 years (range 45 to 87 years). At the12-month follow-up visit, 122 eyes of 81 patientswere available for measurements and examination.One patient died after 6 months of follow-up, and

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another patient had cancer. These eyes were includedin the results up to 6 months.

The mean applied cumulative UV light dose was61.47 G 2.37 J/cm2 (Figures 1 and 2). The numberof adjustments performed was 1.67 G 0.67(Figure 3). Figure 4 shows the mean spherical equiv-alent (SE) refraction postoperatively before the firstadjustment (0.87 G 0.77 D), postoperatively before

OL 37, DECEMBER 2011

Figure 4. Targeted minus achieved SE refrac-tion over time. The bottom and top of thebox are the 25th and 75th percentiles, respec-tively, and the band near the center is the50th percentile (median). The bars outside thebox indicate the maximum and minimum ofall data. The small circles outside the maxi-mum/minimum bars are the outlier data. Aminor outlier (denoted by a small circle) is anobservation 1.5 � interquartile range outsidethe central box. A major outlier (denoted byan asterisk) is seen in the 3.0 � interquartilerange outside the central box.

2098 CORNEAL ENDOTHELIAL CELL LOSS AND THICKNESS WITH LIGHT-ADJUSTABLE IOLS

lock-in (0.27 G 0.31 D), 1 month after lock-in (0.13 G0.29 D), and at the 12-month follow-up (0.13 G 0.31D). Figure 5 shows the relative change in the intrain-dividual ECC from preoperatively to 12 months afterlock-in. The absolute mean endothelial cell count was2288 G 236 cells/mm2, 2131 G 247 cells/mm2, and2136 G 222 cells/mm2 preoperatively, 2 weekspostoperatively before the refractive adjustments ofthe implanted light-adjustable IOLs, and 12 monthsafter lock-in, respectively. Two weeks postopera-tively, before UV light exposure, the mean endothe-lial cell loss was 6.91% G 3.66%, recovering to6.57% G 3.84% 12 months after final lock-in. The de-crease in the ECCwas statistically significant from pre-operatively to postoperatively before adjustment(P!.05) but not from postoperatively to 1 year afterlock-in (PO.05). This indicates that the endothelialcell loss was caused by the cataract surgery, not theUV light exposure, because no additional cell loss

J CATARACT REFRACT SURG - V

was observed after application of UV light for adjust-ments and lock-ins.

The mean CCT increased from 548 G 34 mm preop-eratively to 563 G 43 mm 2 weeks postoperatively be-fore UV light exposure; at 12 months, the mean CCTwas 544 G 35 mm. Figure 6 shows the relative changein mean intraindividual CCT from preoperatively topostoperatively over time. Two weeks postoperativebefore UV light exposure, the mean CCT increaseda mean of 6.18% G 3.97% over preoperative valuesand recovered to preoperative values 1 month to12 months after final lock-in (�0.29% G 2.72 % at1 month; �0.64% G 1.88% 12 months after lock-in).

All cataract surgeries were uneventful. On the firstpostoperative day, 3 eyes had slight corneal edemaat the incision site that resolved with standard therapy(described above) within 4 days. Five eyes hada transient rise in intraocular pressure (IOP) up to24 mm Hg; the IOP decreased to normal values on

Figure 5. Percent endothelial cell loss from pre-operative values over the 1-year follow-up. Thebottom and top of the box are the 25th and 75thpercentiles, respectively, and the band near thecenter is the 50th percentile (median). The barsoutside the box indicate the maximum andminimum of all data. A minor outlier (denotedby a small circle) is an observation 1.5 � inter-quartile range outside the central box. A majoroutlier (denoted by an asterisk) is seen in the 3.0� interquartile range outside the central box.

OL 37, DECEMBER 2011

Figure 6. Relative change in corneal thickness(%) from preoperative values over the 1-yearfollow-up. The bottom and top of the box arethe 25th and 75th percentiles, respectively, andthe band near the center is the 50th percentile(median). The bars outside the box indicate themaximum and minimum of all data. A minoroutlier (denoted by a small circle) is an observa-tion 1.5 � interquartile range outside the centralbox. A major outlier (denoted by an asterisk) isseen in the 3.0 � interquartile range outside thecentral box.

2099CORNEAL ENDOTHELIAL CELL LOSS AND THICKNESS WITH LIGHT-ADJUSTABLE IOLS

the second day after surgery without the need for top-ical antiglaucoma medication.

DISCUSSION

It is well known that UV light exposure to corneas ofdifferent animals or humans can lead to severe andirreversible alterations of different tissues and celllayers. Ringvold et al.13 studied endothelial cellchanges in rabbit corneas using specular and scanningelectron microscopy and found a wide variety ofpathologies. Despite ultrastructural findings even8 months after UV light damage, the endotheliumwas resistant toward repeated radiation damage.Podskochy et al.14 found an increase in corneal cell ap-optosis due to longer wavelength UV light exposure.In 2007, Werner et al.15 published a histological reportto evaluate the corneal endothelial safety with theirradiation doses of UV light at 365 nm using a catmodel. They found no morphologic changes inendothelial cells in the eyes receiving the maximumlock-in dose used to treat light-adjustable IOL com-pared with nonirradiated control eyes.

A recent study by Lichtinger et al.10 reports a meanendothelial cell loss of 12.6% and 9.1% from the preop-erative values in 10 patients 1 week after surgery and6 month after lock-in, respectively. Phacoemulsifica-tion alone leads to endothelial cell loss ranging from4% to 25%, as reported by Mencucci et al.16 The exacttimeframe for endothelial cell recovery ranges from 1to 6 months.17 We believe this is the first report of en-dothelial cell loss and changes in corneal thickness in122 eyes over a 12-month follow-up period after finallock-in. The mean endothelial cell loss from the preop-erative value was 6.91% 2 weeks postoperatively andbefore the refractive adjustments of the implanted

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light-adjustable IOLs and 6.57% 12 months after finallock-in.

Further analysis of cell shape showed no visiblechange in hexagonality at any postoperative visit.Recently published studies assessed the morphologicchanges in corneal endothelial cells resulting fromphacoemulsification alone. Schultz et al.18 found a re-covery of endothelial cell hexagonality 3 months aftercataract surgery. Storr-Paulsen et al.19 compared 2phaco techniques and found no statistically significantchanges in variation in endothelial cell size, percentageof hexagonal cells, or CCTafter 12months of follow-up.

In our group, CCT values increased from a mean of548 mm before surgery to 563 mm 2 weeks postopera-tively before refractive adjustments; this decreased to544 mm 3 months and 12 months after lock-in visits.Mencucci et al.16 report a mean increase in CCT of 3.4mm in 80 eyes 3 months after cataract surgery. Studiesof CCT changes immediately after phacoemulsifica-tion20 found an increase of CCT from 550.34 mm beforesurgery to 626.39mmwithin 1 hour postoperatively, de-creasing to 585.80 mmat 1 day and 553.80 mmat 1week.

The results in this study show that light-adjustableIOL technology by application of spatially profilednear UV light for adjustments and lock-ins makelight-adjustable IOL implantation a safe and stableprocedure for the human cornea. The reported cornealendothelial cell loss was caused by cataract removalwith phacoemulsification. The results after the3-month follow-up suggest that the further decreasewas biological, and no additional effect of UV-lightexposure during refractive corrections was observed.

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First author:Fritz H. Hengerer, MD

Center for Vision Science,Ruhr University Eye Clinic,Bochum, Germany