the impact of tear functions on visual outcome following keratoplasty in eyes with keratoconus

CORNEA

The impact of tear functions on visual outcome followingkeratoplasty in eyes with keratoconus

Shuya Hara & Takashi Kojima & Murat Dogru &

Yuichi Uchino & Eiki Goto & Yukihiro Matsumoto &

Tetsuya Kawakita & Kazuo Tsubota & Jun Shimazaki

Received: 20 September 2012 /Revised: 23 February 2013 /Accepted: 4 March 2013 /Published online: 22 March 2013# Springer-Verlag Berlin Heidelberg 2013

AbstractBackground To investigate the impact of preoperative andpostoperative tear functions on visual outcome and the recov-ery of visual function following keratoplasty in eyes withkeratoconus.Methods Twenty-five eyes of 25 consecutive patients(5 females, 20 males, mean age: 34.3±15.8 years (range: 19–70 years) with keratoconus who underwent either penetratingkeratoplasty (PKP) or deep anterior lamellar keratoplasty(DALK) were included in this prospective study. One patientwho had a rejection episode during the follow-up period wasexcluded. All subjects underwent best corrected visual acuity(BCVA), corneal topography (refractive cylinder, surface reg-ularity index: SRI and surface asymmetry index: SAI),Schirmer I test, tear film break-up time (BUT), corneal sensi-tivity, and fluorescein staining score measurements before aswell as 1, 3, 6 and 12 months after keratoplasty. The relation

between the tear functions and the duration until the achieve-ment of maximum BCVA was also evaluated. Linear regres-sion analysis was performed to study the statistical significanceof the correlations and the time wise change of each examinedparameter.Results SRI, SAI, and BCVA significantly improved afterkeratoplasty. The postoperative corneal sensitivity was stillsignificantly low even at 12 months postoperatively. Postop-erative BCVA at 3, 6 months and maximum BCVA showed asignificant linear negative correlation with the preoperativeBUT (3 months; r=−0.461, p=0.036, 6 months; r=−0.494,p=0.023, maximum BCVA; r=−0.473, p=0.030). The dura-tion until the achievement of maximum BCVA showed asignificant negative correlation with the preoperativeSchirmer test (r=−0.429, p=0.036). BCVA at 1 and 3 monthspostoperatively showed significant linear negative correla-tions with BUT value at the respective periods (1 month;r=−0.665, p=0.0036, 3 months; r=−0.580, p=0.0059).Conclusion Preoperative tear functions appeared to have aninfluence on postoperative BCVA and the duration of visualrecovery in keratoconus patients undergoing keratoplasty.Postoperative tear film stability appears to play an importantrole for obtaining a better BCVA in the early postoperativeperiod after keratoplasty.

Keyword Keratoplasty . Dry eye . Keratoconus . Tearfunctions . Visual recovery

Introduction

Penetrating keratoplasty (PKP) and deep anterior lamellarkeratoplasty (DALK) have been traditionally performed as atreatment for corneal perforation, corneal opacity induced by

Presented at: the 2007 ARVO Annual Meeting, Fort Lauderdale,Florida, U.S.A., May 6–10, 2007

S. Hara : T. KojimaDepartment of Ophthalmology, Social InsuranceChukyo Hospital, Nagoya-shi, Aichi, Japan

T. Kojima :M. Dogru :Y. Uchino : E. Goto :Y. Matsumoto :T. Kawakita :K. TsubotaDepartment of Ophthalmology, Keio University, Tokyo, Japan

M. Dogru :Y. Uchino : E. Goto :Y. Matsumoto : T. Kawakita :J. ShimazakiDepartment of Ophthalmology, Tokyo DentalCollege, Chiba, Japan

M. Dogru (*)School of Medicine, Keio University, Shinanomachi35 Shinjuku-ku, Tokyo, Japane-mail: [email protected]

Graefes Arch Clin Exp Ophthalmol (2013) 251:1763–1770DOI 10.1007/s00417-013-2307-6

infection or trauma, corneal dystrophy, and keratoconus, inwhich the area of disease reaches the stroma with or withoutendothelial involvement [1–4].

Several months are necessary to achieve stable visualfunctions after PKP and DALK, and the periods of the visualrecovery after surgeries for individual cases are variable[4–11]. The duration until the achievement of maximum bestcorrected distance visual acuity (BCVA) has been reported tobe influenced by the original disease and induced astigmatism[4–11]. Because early visual recovery affects satisfaction ofpatients after surgery, several proposals for management ofinduced astigmatism have been reported [4–11].

Ocular surface abnormalities with positive vital stainingare commonly seen in the patients after PKP or DALK.Although tear film abnormalities and superficial punctatekeratitis (SPK) have been reported to influence visual symp-toms [12–19], the effect of tear functions on visual recoveryafter PKP or DALK has not been clarified so far.

In this study, we investigated the impact of preoperativeand postoperative tear functions on visual outcome andrecovery following PKP or DALK in eyes with keratoconus.

Patients and methods

Twenty-five eyes of 25 consecutive keratoconus patients whofailed fitting with rigid gas-permeable contact lenses andunderwent keratoplasty from July 2005 to December 2005were enrolled in this single center prospective study. Thisstudy was registered at the data base of Tokyo Dental College.This study included 5 females and 20 males with a mean ageof 34.3±15.8 years (range; 19–70 years). All patients receivedfull explanation about the purpose of this study as well asadvantages and disadvantages of both PKP and DALK. Westrictly adhered to the tenets of the Helsinki Declaration andreceived full written informed consent from all participants.Study examination procedures were ethic board reviewed.Keratoconus patients without atopic disease, lid congruitydisorders, meibomian gland disease and blepharitis were in-cluded. None of the participants had a systemic disorder,cataract, retinal disease, amblyopia, or other ocular diseasesthat would have influenced the visual outcome. Patients with ahistory of other ocular surgery or systemic drug use within6 months before the surgery, patients with rejection episodeafter the surgery were also excluded from the study.

The follow up period after the surgery was 12 months.DALK was initially attempted in 7 consecutive eyes withcorneal endothelial cells more than 1,500 cells/mm2 and nohistory of acute hydrops, however 3 cases were convertedinto PKP during the surgery because of perforation ofDescemet membrane. Therefore, DALK was finally per-formed in 4 eyes and PKP was totally performed in 21 eyes.Neither PKP nor DALK were performed with any other

complications except for the perforation of Descemet mem-brane mentioned above.

Surgical methods

1. Penetrating keratoplasty (PKP)Donor corneas with the same size or 0.25 mm larger

in diameter than the recipient trephination size (7.5 mm)were punched out using a Barron donor punch (KatenaProducts Inc., Denville, New Jersey, USA). The corneaswere secured to the recipient’s eye following excision ofthe abnormal corneas using a Hessburg-Barron trephine(Katena). A single continuous running suture using 10–0 nylon was performed. At the end of surgery, intra-operative suture adjustment to reduce induced cornealastigmatism was performed.

2. Deep anterior lamellar keratoplasty (DALK)Recipient 7.5 mm corneal stromas were trephinated

1/2-2/3 in depth using a Hessburg-Barron trephine. Cor-neal tunnel was dissected extending 1.0 mm into the clearcornea by lamellar surgical knives (Ultrasharp microsur-gical knives, No. 681.01 and 681.25, Grieshaber, Switzer-land). A spatula was inserted through the corneal pocketand advanced into the deep stroma until the mirror reflexof the tip of the spatula showed a fine line to indicate aresidual corneal stromal bed up to Descemet membranewas little [20]. The Descemet membrane was kept awayfrom the overlying stroma using an air or balanced salinesolution before the residual stromal excision. The donorendothelium and Descemet membrane (following0.25 mm-oversized trephination using Barron donorpunch) were dissected using a toothed forceps (Ultrafinenotched forceps F240W, Inami, Tokyo, Japan) andspring- type micro-scissors (S-551C, Inami, Japan). Thedonor buttons were secured by a single continuous 10–0nylon suture. At the end of surgery, intraoperative sutureadjustment was performed in the same fashion as in PKP.

Post surgical management

Bandage soft contact lenses were placed until the cornealepithelial defects resolved in slitlamp examination. All eyesreceived topical antibiotics (ofloxacin, Tarivid, Santen Phar-maceutical Co., Osaka, Japan) and 0.1 % betamethasone(Sanbetason, Santen) five times a day. Only when high regularcorneal astigmatism was seen within 3 week after the surgery,an additional adjustment for the astigmatism by tucking thecontinuous running suture was performed. When an irregularcorneal surface persisted for more than 3 weeks after thesurgery in slitlamp examination, patients received preserva-tive free artificial tear drops containing 0.1 % KCl and 0.4 %NaCl (Softsantear, Santen Pharmaceutical Co. Ltd., Osaka,Japan) 4–6 times daily, 0.1 % hyaluronic acid (preservation

1764 Graefes Arch Clin Exp Ophthalmol (2013) 251:1763–1770

free Hyalein mini 0.1 %, Santen) 4–6 times daily, and autol-ogous serum 4–6 times daily. Until 12 months after surgery,removal of the stitches was performed only when the contin-uous running sutures were redundant or snapped.

Visual and tear functions measurement

Best corrected distance visual acuity (BCVA) was measuredand the duration until the achievement of the maximumBCVA was evaluated. Corneal topography was performedusing the TMS-2 (Tomey Corporation, Nagoya, Japan). Thesurface regularity index (SRI) and surface asymmetry index(SAI) and corneal astigmatism that were calculated by theinstrument’s software were recorded for all participants [21].The standard tear film break up time (BUT) measurementwas performed as reported previously [22, 23] after instilla-tion of 2 μl of 1 % fluorescein with preservation freesolution under the slit lamp examination. After the BUTmeasurement, fluorescein staining score measurement ofthe cornea divided into three parts; upper, middle and lowerwas performed. Each corneal part was graded as: grade 0, no

staining; grade 1, mild staining; grade 2, staining betweengrades 1 and 3; grade 3, severe staining. The scores of threeparts were added. The standard Schirmer I test withouttopical anesthesia was performed at least more than15 min after the fluorescein staining score measurement.The sterilized strips of filter paper (Schirmer test paper,Showa Yakuhin Kako Co, Ltd, Tokyo, Japan) was placedin the lateral canthus and left for 5 min. Corneal sensitivitywas measured using a Cochet-Bonnet esthesiometer.

These measurements were performed before as well as 1, 3,6 and 12 months after keratoplasty in the same order for allpatients. Relations between the speed of visual recovery,postoperative visual outcomes at each period and preoperativetear functions were investigated. Relations between postoper-ative tear functions, topographic indices and postoperativevisual outcomes at the same period were also investigated.All tear function examinations were performed during thesame morning hours at each follow up visit. Patients hadinstilled their eye medications before going to sleep who thenunderwent the tear function examinations before initiatingtheir eye drops on the day of the visit.

-0.5

0

0.5

1

1.5

2

2.5

Before surgery 1 month 3 months 6 months 1 year

Mea

n B

CV

A (

logM

AR

)

Postoperative period

Fig. 1 The change of bestcorrected distance visual acuity(BCVA) before and aftersurgery. The mean BCVA(logMAR) ± standard deviationwas 1.46±0.47 before surgery,which improved to 0.42±0.29,0.23±0.20, 0.17±0.16 and 0.14±0.24 at 1, 3, 6 and 12 monthsafter surgery

-1

0

1

2

3

4

5

6

7

Before surgery 1month 3 months 6months 1 year

Cor

neal

sen

sitiv

ity (

mm

)

Postoperative period

***

*

Fig. 2 The change of cornealsensitivity before and aftersurgery. Postoperative cornealsensitivity at each examinationpoint was significantly lowerthan the preoperative value

Graefes Arch Clin Exp Ophthalmol (2013) 251:1763–1770 1765

Statistical analysis

Graphpad Prism (GraphPad Software Inc, CA, USA) soft-ware was used for statistical analysis. Kruskal-Wallis testwas performed to analyze the statistical significance of timewise change of each examined parameter. Linear regressionanalysis was performed to analyze correlations betweenexamined parameters. A P value of less than 0.05 wasconsidered to be statistically significant.

Results

In the patients undergoing DALK, no eyes showed doubleanterior chamber due to the detachment of Descemet mem-brane more than 2 weeks after the surgery. Three patientsexperienced a temporary increase in intraocular pressurethroughout the study, which finally decreased to the preoper-ative level with application of oral acetazolamide (Diamox,Lederle Parenterals, Inc., Carolina, Puerto Rico). One patientwho had an immunologic rejection episode was excludedfrom this study. In all 25 eyes, BCVA improved after kerato-plasty and clear corneal grafts were achieved in all eyes. Themean BCVA (logMAR)±standard deviation was 1.46±0.47before the surgery, which improved to 0.42±0.29, 0.23±0.20,0.17±0.16 and 0.14±0.24 at 1, 3, 6 and 12 months after thesurgery, respectively (Fig. 1).

Changes of tear functions and corneal sensitivity

Mean postoperative corneal sensitivity at each examinationpoint after surgery was significantly lower than the preop-erative value (p<0.001) (Fig. 2). The SRI and the SAIsignificantly improved at 1 month after surgery and werestill improved at 3, 6 and 12 months in comparison with thepreoperative value (p<0.0001). There were no statisticallysignificant time wise changes of the mean Schirmer testvalue, the BUT, the fluorescein staining score, and thecylinder on the corneal topography at each examinationpoint before and after keratoplasty (Table 1).

Correlation between preoperative tear functionsand postoperative visual outcome

The postoperative BCVA at 3, 6 months and maximum BCVAshowed a significant linear negative correlation with the preop-erative BUT (3 months; r=−0.461, p=0.036, 6 months;r=−0.494, p=0.023, maximum BCVA; r=−0.473, p=0.030).There were no statistically significant correlations betweenother preoperative parameters (the corneal sensitivity, theSchirmer test value, and the fluorescein score) and the post-operative BCVA, maximum BCVA during the follow-up pe-riod. However, the duration until the achievement ofT

able

1Postoperativ

echangesof

tear

functio

nsandcornealtopo

graphy

indices

Schirmer

testvalue

BUT

Fluorescein

score

Cylinderon

corneal

topo

graphy

SRI

SAI

Measurement

value

Pvalue

*Measurement

value

Pvalue

*Measurement

value

Pvalue

*Measurement

value

Pvalue

*Measurement

value

Pvalue*

Measurement

value

Pvalue*

Preop

erative

17.9±12

.5–

5.71

±3.23

–0.83

±1.72

–4.09

±2.20

–3.22

±0.50

–3.52

±1.56

–

1mon

thpo

stop

erative

19.7±11.5

NS

6.00

±2.78

NS

1.45

±1.50

NS

4.75

±1.81

NS

2.24

±0.56

<0.00

01*

1.99

±0.90

<0.00

01*

3mon

thpo

stop

erative

17.5±11.8

NS

6.95

±2.91

NS

0.59

±0.67

NS

4.58

±2.58

NS

2.10

±0.53

<0.00

01*

1.67

±0.69

<0.00

01*

6mon

thpo

stop

erative

20.4±13

.3NS

6.27

±2.89

NS

0.39

±0.61

NS

4.02

±2.49

NS

1.89

±0.60

<0.00

01*

1.71

±0.79

<0.00

01*

12mon

thpo

stop

erative

17.4±12

.7NS

6.64

±2.98

NS

0.35

±0.70

NS

4.23

±2.75

NS

1.74

±0.65

<0.00

01*

1.46

±0.96

<0.00

01*

BUTtear

film

break-up

time,SR

Isurfaceregu

larity

index,

SAIsurfaceasym

metry

index,

NSno

tsign

ificant

*Representsstatistically

sign

ificantdifference

betweenpreoperativ

eandeach

postop

erativeperiod


maximum BCVA significantly correlated with preoperativeSchirmer test value (r=−0.429; p=0.036) (Table 2). The pre-operative Schirmer test value showed a statistically significantcorrelation with the SRI 1 month after surgery (r=−0.452;p=0.031) (Table 3).

Correlation between postoperative tear functionsand postoperative visual outcome

The BUT at 1 and 3 months after surgery showed significantlinear negative correlations with the BCVA (1 month;r=−0.665; p=0.0036 and 3 months; r=−0.580; p=0.0059)

(Table 4). Especially the postoperative BUT at 3 monthsshowed a significant linear negative correlation with the SAIat the same period (r=−0.463; p=0.040) (Table 5).

Discussion

PKP and DALK may be disadvantageous in that thesemethods need a long time for visual recovery after thesurgery because the grafts for PKP and DALK includecorneal epithelium which takes time to obtain a smoothcorneal surface with a high refractive stability. Although

Table 2 Correlations between preoperative tear functions and postoperative visual outcome

Preoperative cornealsensitivity

Preoperative Schirmertest value

Preoperative BUT Preoperativefluorescein score

Correlationcoefficient:r

P value*


P value*


P value*


P value*

1 month postoperative BCVA −0.192 0.393 −0.224 0.293 −0.375 0.094 0.043 0.846

3 month postoperative BCVA 0.304 0.170 −0.339 0.105 −0.461 0.036* −0.370 0.082

6 month postoperative BCVA 0.100 0.659 −0.292 0.166 −0.494 0.023* −0.094 0.670

12 month postoperative BCVA 0.134 0.608 −0.188 0.455 −0.434 0.093 −0.126 0.619

Maximum BCVA throughout the study 0.099 0.662 −0.092 0.669 −0.473 0.030* −0.255 0.240

Duration until the attainment ofmaximum BCVA

0.274 0.217 −0.429 0.036* 0.092 0.691 −0.340 0.113

BCVA best corrected visual acuity, BUT tear film break-up time

* Represents statistically significant correlation between preoperative parameters and postoperative visual outcome

Table 3 Correlations between preoperative tear functions and postoperative corneal topography indices

Preoperative Schirmer testvalue

Preoperative BUT Preoperative fluoresceinscore

Correlationcoefficient: r

P value * Correlationcoefficient: r


P value *

1 month postoperative cylinder on corneal topography 0.178 0.418 0.416 0.068 −0.075 0.740

3 month postoperative cylinder on corneal topography 0.027 0.905 0.430 0.066 0.118 0.610

6 month postoperative cylinder on corneal topography −0.185 0.449 0.216 0.389 0.353 0.138

12 month postoperative cylinder on corneal topography 0.061 0.836 0.268 0.399 −0.523 0.055

1 month postoperative SRI −0.452 0.031* −0.123 0.607 0.045 0.844

3 month postoperative SRI −0.166 0.461 0.151 0.537 −0.112 0.629

6 month postoperative SRI 0.108 0.660 0.037 0.885 0.084 0.731

12 month postoperative SRI −0.077 0.785 −0.047 0.879 0.120 0.670

1 month postoperative SAI −0.301 0.164 −0.059 0.805 0.109 0.631

3 month postoperative SAI −0.360 0.100 −0.086 0.727 −0.133 0.566

6 month postoperative SAI 0.231 0.372 0.266 0.321 0.296 0.249

12 month postoperative SAI −0.031 0.914 −0.129 0.675 0.316 0.251

BUT tear film break-up time, SRI surface regularity index, SAI surface asymmetry index

* Represents statistically significant correlation between preoperative and postoperative parameters


the influence of the astigmatism induced from the suturingof the graft on the visual outcome has often been described[5–11], the influence of tear functions on the visual recoveryhas not been clarified. In this study, we investigated theinfluence of tear functions before and after the surgery onthe visual outcome after PKP and DALK. Only patients ofkeratoconus are enrolled in this study so that the variety ofthe primary diagnoses would not affect the visual outcomeand the measurement of tear functions.

There were no significant changes in the refractive cylinderon corneal topography at any period before and after thesurgery. The refractive cylinder did not increase even 1 monthafter surgery because suture adjustment was performed toreduce the induced astigmatism during and within 3 weeksafter the surgery. Since regular astigmatism expressed by therefractive cylinder is more correctable with glasses in com-parison with irregular astigmatism [24–26] and all subjectshad the same preoperative diagnosis (keratoconus), we believethat the influence of astigmatic cylinder and the preoperativediagnosis on postoperative BCVA should be negligible. The

elimination of the irregularity of the corneal refraction, whichis provided by the attainment of a smooth corneal surface, is apossible explanation for the continuous improvement of SRI,SAI, and BCVA.

In this study, we investigated the influence of the preoper-ative tear functions on the postoperative visual outcome. Al-though the preoperative Schirmer test value, the fluoresceinscore and the corneal sensitivity did not affect the postoperativeBCVA, the BCVA at 3, 6 months after surgery and the maxi-mum BCVA throughout the study became significantly betteras the preoperative BUT was longer. The duration until theattainment of the maximum BCVA became significantlyshorter as the preoperative Schirmer test value was higher.SRI 1 month after surgery showed a more significant improve-ment in patients with a higher preoperative Schirmer value.Based on this result, it can be suggested that patients with ahigher preoperative tear stability appear to achieve a betterpostoperative BCVA after keratoplasty, and those who with ahigher preoperative tear production appear to achieve an earliervisual recovery after the surgery because of the prompt

Table 4 Correlations between postoperative tear functions and BCVA

Schirmer test value BUT Fluorescein score

CorrelationCoefficient: r

P value * CorrelationCoefficient: r

P value * CorrelationCoefficient: r

P value *

BCVA vs tear functions at 1 monthpostoperative

0.087 0.740 −0.665 0.0036* 0.077 0.726


−0.354 0.137 −0.580 0.0059* 0.102 0.652


−0.451 0.122 −0.325 0.238 0.04 0.868


−0.228 0.433 −0.451 0.106 −0.031 0.902

BCVA best corrected visual acuity, BUT tear film break-up time

* Represents statistically significant correlation between parameters at the same period

Table 5 Correlations betweenpostoperative tear functions andcorneal topography indices

BUT tear film break-up time, SRIsurface regularity index, SAIsurface asymmetry index

* Represents statistically signifi-cant correlation between param-eters at the same period

Schirmer test value BUT

Correlationcoefficient: r


P value *

SRI vs tear functions at 1 month postoperative −0.411 0.114 −0.414 0.011

SRI vs tear functions at 3 month postoperative 0.115 0.650 −0.206 0.384

SRI vs tear functions at 6 month postoperative 0.275 0.363 0.449 0.093

SRI vs tear functions at 12 month postoperative 0.000 0.999 −0.247 0.415

SAI vs tear functions at 1 month postoperative 0.292 0.272 −0.363 0.167

SAI vs tear functions at 3 month postoperative −0.223 0.374 −0.463 0.040*

SAI vs tear functions at 6 month postoperative 0.132 0.682 0.450 0.107

SAI vs tear functions at 12 month postoperative 0.198 0.517 −0.465 0.109


attainment of a smooth corneal surface. Further investigationsof the relationship between wound healing after keratoplastyand visual recovery are needed.

We also investigated the influence of the postoperative tearfunctions on the postoperative visual outcome. The BCVA 1and 3 months after surgery significantly improved in subjectswith higher BUT values at those examination points. Eyeswith a longer BUT 3 months after surgery achieved lower SAIvalues, which suggests that the postoperative tear film stabilityhas an important role in the achievement of better BCVAvalues in the early postoperative period.

There are several limitations in the current study. Weperformed only bivariate correlation analysis due to smallnumber of cases. Since the confounding parameters areincluded, Cox’s proportional hazards model should be per-formed in the future study including larger number of cases.

Many previous studies reported a decline in corneal sensi-tivity after PKP and DALK [27–30]. Darwish et al. reported adecrease in BUT without any changes in tear quantity afterkeratoplasty [30]. They suggested the nerve fibers in theperipheral recipient cornea might be sufficient for the preser-vation of neural feedback loop to control the tear production.

In our study, we found a decrease in corneal sensitivityafter keratoplasty without any changes in tear stability andquantity.

The discrepancy in the outcomes between the previousreport and ours might have resulted from the differences inage, gender, graft sizes, and the preoperative diagnoses.

One limitation of our study was that eyes after twodifferent surgeries (PKP and DALK) were enrolled in thestudy. Although Shimazaki et al [4] described there were nosignificant differences in the speed of the visual recoveryand the final BCVA between patients after PKP and DALK,potential differences such as nerve reinnervation and cornealhigher order aberrations may have affected our results.

In summary, the present study revealed the impact ofpreoperative tear functions on postoperative BCVA andearly visual outcome after keratoplasty. To achieve a highersatisfaction in patients after keratoplasty, an adequate treat-ment of preoperative dry eye and postoperative control oftear film stability may have an important role in visualrehabilitation after keratoplasty. Since previous studiesrevealed that dry eye disease affected higher order aberra-tions, further studies evaluating the correlation betweenpostoperative higher order aberrations and visual outcomeafter keratoplasty will help understanding the mechanism ofearly visual recovery following PKP and DALK.

Commercial relationship disclosure None

Grant support None

References

1. Arentsen JJ (1983) Corneal transplant allograft reaction: possiblepredisposing factors. Trans Am Ophthalmol Soc 81:361–402

2. Ing JJ, Ing HH, Nelson JR, Hodge DO, BourneWM (1998) Ten-yearpostoperative results of penetrating keratoplasty. Ophthalmology105:1855–1865

3. Sugita J, Kondo J (1997) Deep lamellar keratoplasty with completeremoval of pathological stroma for vision improvement. Br JOphthalmol 81:184–188

4. Shimazaki J, Shimmura S, Ishioka M, Tsubota K (2002)Randomized clinical trial of deep lamellar keratoplasty vs pene-trating keratoplasty. Am J Ophthalmol 134:159–165

5. McNeill JI, Aaen VJ (1999) Long-term results of single continuoussuture adjustment to reduce penetrating keratoplasty astigmatism.Cornea 18(1):19–24

6. Shimazaki J, Shimmura S, Tsubota K (1998) Intraoperative versuspostoperative suture adjustment after penetrating keratoplasty.Cornea 17(6):590–594

7. Tsubota K, Kaido M, Monden Y, Satake Y, Bissen-Miyajima H,Shimazaki J (1998) A new surgical technique for deep lamellarkeratoplasty with single running suture adjustment. Am JOphthalmol 126(1):1–8

8. Karabatsas CH, Cook SD, Figueiredo FC, Diamond JP, Easty DL(1998) Combined interrupted and continuous versus single contin-uous adjustable suturing in penetrating keratoplasty: a prospective,randomized study of induced astigmatism during the first postop-erative year. Ophthalmology 105(11):1991–1998

9. Riddle HK Jr, Parker DA, Price FW Jr (1998) Management ofpostkeratoplasty astigmatism. Curr Opin Ophthalmol 9(4):15–28

10. Javadi MA, Naderi M, Zare M, Jenaban A, Rabei HM, Anissian A(2006) Comparison of the effect of three suturing techniques onpostkeratoplasty astigmatism in keratoconus. Cornea 25(9):1029–1033

11. Vinciguerra P, Epstein D, Albè E, Spada F, Incarnato N, OrzalesiN, Rosetta P (2007) Corneal topography-guided penetrating kera-toplasty and suture adjustment: new approach for astigmatismcontrol. Cornea 26(6):675–682

12. Khanal S, Tomlinson A, McFadyen A, Diaper C, Ramaesh K(2008) Dry eye diagnosis. Invest Ophthalmol Vis Sci 49(4):1407–1414

13. Wilson SE, Stulting RD (2007) Agreement of physician treatmentpractices with the international task force guidelines for diagnosisand treatment of dry eye disease. Cornea 26(3):284–289

14. Wang HF, Fukuda M, Shimomura Y (2005) Diagnosis of dry eye.Semin Ophthalmol 20(2):53–62

15. Perry HD, Donnenfeld ED (2004) Dry eye diagnosis and manage-ment in 2004. Curr Opin Ophthalmol 15(4):299–304

16. Dogru M, Tsubota K (2004) New insights into the diagnosis andtreatment of dry eye. Ocul Surf 2(2):59–75

17. KaidoM, DogruM, Ishida R, Tsubota K (2007) Concept of functionalvisual acuity and its applications. Cornea 26(9 Suppl 1):S29–S35

18. Goto E, Ishida R, Kaido M, Dogru M, Matsumoto Y, Kojima T,Tsubota K (2006) Optical aberrations and visual disturbancesassociated with dry eye. Ocul Surf 4(4):207–213

19. Goto E, Yagi Y, Matsumoto Y, Tsubota K (2002) Impaired func-tional visual acuity of dry eye patients. Am J Ophthalmol 133(2):181–186

20. Melles GR, Rietveld FJ, Beekhuis WH, Binder PS (1999) Atechnique to visualize corneal incision and lamellar dissectiondepth during surgery. Cornea 18:80–86

21. Kojima T, Ishida R, Dogru M, Goto E, Takano Y, Kaido M, OhashiY, Tsubota K (2004) A new noninvasive tear stability analysissystem for the assessment of dry eyes. Invest Ophthalmol Vis Sci45(5):1369–1374


22. Toda I, Tsubota K (1993) Practical double vital staining for ocularsurface evaluation. Cornea 12:366–367

23. Shimmura S, Ono M, Shinozaki K, Toda I, Takamura E, MashimaY, Tsubota K (1995) Sodium hyaluronate eyedrops in the treatmentof dry eyes. Br J Ophthalmol 79:1007–1011

24. Wyzinski P (1990) Escalation of keratospeak: regular and irregularastigmatism. Refract Corneal Surg 6:231

25. Azar DT, Strauss L (1994) Principles of applied clinical optics. In:Albert DM, Jakobiec FA (eds) Principles and practice of ophthal-mology, vol 5. WB Saunders, Philadelphia, pp 3603–3621

26. Troutman RC, Buzard KA (1992) Corneal astigmatism. Etiology,prevention, and management. Mosby Year Book, St. Louis, pp 5–22

27. Ceccuzzi R, Zanardi A, Fiorentino A, Tinelli C, Bianchi PE (2010)Corneal sensitivity in keratoconus after penetrating and deep ante-rior lamellar Keratoplasty. Ophthalmologica 224(4):247–250

28. Shimazaki J, Shimmura S, Mochizuki K, Tsubota K (1999)Morphology and barrier function of the corneal epithelium afterpenetrating keratoplasty: association with original diseases, tearfunction, and suture removal. Cornea 18(5):559–564

29. Tuğal Tutkun I, Akarçay K, Közer Bilgin L, Sansoy N,Urgancioğlu M (1993) Corneal sensitivity after penetrating kera-toplasty. Eur J Ophthalmol 3(2):66–70

30. Darwish T, Brahma A, Efron N, O’Donnell C (2007) Subbasal nerveregeneration after penetrating keratoplasty. Cornea 26:935–940


the impact of tear functions on visual outcome following keratoplasty in eyes with keratoconus

Documents