181 patients operated for optical p.k . at our institute between october 2005 and october 2007 and those who completed at least one - year follow - up were included for analysis . in patients who underwent multiple p.k.s , or bilateral p.k.s , ( at our institute )
patients presenting with failed grafts , who had undergone one or more grafts somewhere else , were included in analysis as previous failed grafts .
exclusion criteria were pediatric cases , therapeutic , tectonic , lamellar grafts , and patients who followed up for less than a year . based on the preoperative diagnosis [ table 1 ]
good prognosis , which included quiet eyes with inactive corneal scars , corneal degenerations , and dystrophies with no corneal vascularization ; fair prognosis , which included patients of aphakic or pseudophakic bullous keratopathy , adherent leucomas , and corneal scars following perforations , descemetoceles .
poor prognosis category consisted of congenital corneal scars , preexisting glaucoma , unstable ocular surface , postchemical injury corneal scars , post- herpes simplex keratitis ( hsv ) keratitis corneal scars , and all eyes with > 2 quadrants deep vessels .
the patients operated for congenital hereditary endothelial dystrophy(ched ) or congenital corneal scars were bilaterally blind , so after explaining about guarded visual prognosis ( due to amblyopia ) , these patients were operated with expectation of gaining ambulatory vision postoperatively .
indications for penetrating keratoplasty in situ corneoscleral rim excision was done for all eye donations and donor tissue was collected in m.k .
tissue was labeled as excellent quality if epithelium was intact , stroma compact without any opacities or haze , no descemet 's membrane ( dm ) folds , and endothelial cell density ( ecd ) > 2 500 ; good quality if minimal exposure keratitis was present with light stromal haze , few dm folds , and ecd between 2 000 and 2 500 ; and fair quality if significant exposure was present , moderate degree of stromal haze with central dm folds , and ecd between 1 800 and 2 000 .
tissue evaluation was done by slit lamp observation and with bioptics lsm 12000 specular microscope , by ophthalmologists who had done their fellowship training in cornea .
surgeries were done by two equally experienced surgeons who had done their fellowship training . in all cases ,
the donor grafts were 0.5 mm larger than the recipient . commonly used graft sizes were 8.0  7.5 mm , 7.5  7.0 , and 8.5  8.0 mm .
we used the manual disposable trephines for all cases . in all cases , interrupted suturing with 10/0 nylon was done .
triple ( pk with cataract extraction with iol ) , or pk with additional surgery like ( anterior vitrectomy , pupilloplasty , intraocular lens explant , etc . ) for further analysis [ table 2 ] .
postoperatively , patients were given prednisolone acetate ( 1% ) eye drops , topical antibiotics , and artificial tears , antiglaucoma drugs if needed .
routine follow - up schedule was every weekly for first month , biweekly for second month , monthly for 3 to 6 months , and every three months for one year .
 penetrating keratoplasties and associated procedures selective suture removal was started from third month onward , after assessing tightness of sutures on slit lamp examination , and calculating astigmatism by retinoscopy , keratometry , or topography .
graft rejection was defined as presence of one or more of the following signs : mild if there were 1 to 5 keratic precipitates ( kp ) , sub epithelial infiltrates , increased corneal thickness without increase in aqueous cells ; severe rejection if > 5 kps , inflammatory cells in the stroma ( not due to infection ) , endothelial rejection line , or increased thickness with aqueous cells .
graft clarity was graded as grade 4 if grafts were optically clear with excellent view of iris details , grade 2 - 3 ( borderline ) if there was moderate to significant corneal haze with or without good view of iris details , and grade 1 - 0 ( failed ) for opaque grafts with poor view of iris and anterior segment details .
good visual improvement was defined as postoperative vision improvement two lines on snellen 's compared with preoperative vision , moderate as one line improvement , and no improvement if vision remained same or worsened .
graft failure was defined as irreversible loss of optical clarity with the date of onset taken when the patient presented to cornea clinic with signs of irreversible rejection ( for 3 months or more ) or with failed graft .
patients with no graft failure during follow - up period were considered as  censored cases . 
kaplan - meier survival analysis was performed to calculate median survival ( failure free ) time of the grafts [ table 3 ] .
age , gender , corneal vascularization , previous failed grafts , hsv keratitis , post - perforation corneal scars , donor tissue quality , graft size and type of surgery , and postoperative glaucoma .
log rank statistics was used to test the equality of estimates of survival functions among different strata of above correlates .
univariate and multivariate cox proportional hazards models were used to assess the relationship between risk factors and graft failure event [ table 4 ] .
results were considered as significant with a two - sided p value of < 0.05 .
kaplan meier survival analysis univariate and multivariate cox regression models for risk factors predicting graft failure
of 181 patients , 125 ( 69.1% ) were males and 56 ( 30.93% ) females .
patients were followed for median follow - up of 9 months ( inter quartile range ( iqr ) : 3 - 15 months duration ) .
114 ( 63% ) patients had preoperative vision of light perception and projection of rays ( plpr ) and 67 ( 37.1% ) had better than plpr vision . of 181 patients , 120 completed at least one year of follow - up . at one year
, 77 ( 64.16% ) grafts remained optically clear ( grade 4 clarity ) , 11 ( 9.16% ) had borderline clarity ( grade 2 - 3 ) , and 32 ( 26.66% ) grafts failed .
good visual improvement was seen in 59 ( 49.17% ) , moderate visual improvement in 25 ( 20.83% ) , and vision did not improve in 36 ( 30% ) . of 181 patients
eleven patients did not even come for the first follow - up ; therefore , these cases were excluded . since the event of interest in survival analysis is graft failure , for the remaining 170 cases , estimation of survival function was possible even though some of them did not complete one year of follow - up .
of 170 patients , graft failure was observed among 54 ( 31.76% ) patients during two - year follow - up period .
median survival of grafts in the cohort was 27 months ( 95% confidence interval [ ci ] : 20.47  33.52 ) .
65% of the grafts survived at 12 months , whereas 52.5% of the grafts survived at 24 months [ fig . 1 ] .
kaplan meier curve for graft failure graft survival did not differ between 2 gender groups ( male  23 months , females - 30 months , p = 0.119 ) and also between 2 recipient age groups ( < 60 years - 29 months , > 60 years - 27 months , p = 0.950 ) .
graft survival in good prognosis cases was 27 months ( 95% ci : 20.42 - 33.52 ) and in poor prognosis cases was 14 months ( 95% ci : 6.26 - 21.73 , p = 0.045 ) [ fig . 2 ] .
prognosis vs graft survival the prognosis of the case was determined on the basis of prior corneal vascularization , preexisting corneal perforation followed by scaring , history of herpes simplex keratitis ( hsk ) , and history of previous ipsilateral corneal graft .
the extent of vascularization of recipient bed correlates strongly with the graft survival , as demonstrated in the australian corneal graft registry ( acgr ) report so , we used quadrants of vascularization as one of the factors for grouping our cases into fair prognosis ( intermediate risk ) category and poor prognosis ( high risk ) category .
in order to study the relation between individual risk factors like vascularization and graft survival , rather than low - risk vs high - risk group , our further analysis is designed accordingly . in eyes with more than two quadrants of vascularization ( n = 45 ) , and those with less than two quadrants of vascularization ( n = 48 ) , median graft survival was 18.55 months ( 95% ci : 15.6  21.4 ) . in nonvascularized corneas ( n = 77 ) ,
in corneal scars following perforation ( n = 72 ) , graft survival was 17.96 months  1.43 ( 95% ci : 15.14  20.78 ) , whereas cases in which there was no perforation ( n = 98 ) , median graft survival was 22.56 months  1.403 ( 95% ci : 19.81 - 5.31 , p = 0.09 , borderline significant ) [ fig . 4 ] . in post - hsv keratitis cases
( n = 13 ) , graft survival was 16.9 months ( 95% ci : 11.56 - 22.27 ) , whereas in non - hsv keratitis ( n = 157 ) , graft survival was 20.95 months ( 95% ci : 18.72 , 23.73 , p = 0.544 ) [ fig .
5 ] . in previous failed grafts ( one or more grafts done elsewhere ) ( n = 21 ) , median graft survival was 14 months ( 95% ci : 5.55 - 22.44 months ) .
this was much lower than eyes with first - time grafts ( n = 149 ) in which median graft survival was 27 months ( 95% ci : 21.11  32.88 ) ; however , this difference was not statistically significant ( p = 0.207 ) [ fig . 6 ] . in eyes with postoperative glaucoma ,
the median graft survival was 18.35 months ( 95% ci : 13.94 - 22.76 ) as compared with eyes without postoperative glaucoma ( median , 21.59 months ; 95% ci : 19.30 - 23.88 ) .
graft survival in vascularized corneas graft survival in corneal perforations graft survival in hsv corneal scars graft survival in previous failed grafts postoperative glaucoma in our study , cases for which very good quality donor corneas ( n = 8) were used , had longer graft survivals ( 25.42 months ) as compared with other cases ( n = 147 , good quality graft ; n = 15 , fair quality grafts ) , but this difference was not statistically significant ( p = 0.41 ) [ fig .
donor tissue quality vs graft survival in our series , we found that graft survival did not differ significantly in small size grafts ( 7.5  7 mm ) ( n = 66 ) , medium size ( 8  7.5 mm ) ( n = 85 ) , or large size grafts ( 8.5  8 mm ) ( n = 19 ) ( p = 0.549 ) [ fig . 9 ] .
graft size vs graft survival graft survival did not differ statistically ( p = 0.303 ) in different types of surgeries namely pk , ( n = 62 ) , pk triple ( n = 68 ) , and pk with additional surgery ( n = 40 ) [ fig . 10 ] .
additional surgeries included anterior vitrectomy ( 15 ) , pupilloplasty ( 4 ) , conjunctival limbal autografts ( 6 ) , and iol explants / exchanges ( 15 ) .
type of surgery vs graft survival in patients who followed up regularly ( n = 64 ) , medial graft survival time was 27 months ( 95% ci : 20.43 - 33.56 months ) as compared with irregular follow ups ( n = 106 ) in whom median graft survival time was 11 months ( 95% ci : 4.28 - 17.71 months , p = 0.001 ) [ fig .
follow - up vs graft survival table 3 summarizes the median survival time in months of corneal grafts and association between covariates and graft failure .
kaplan meier multivariate cox proportional hazard regression analysis was performed to evaluate the combined effect of ten risk factors [ table 4 ] . of these , vascularization ( p = 0.048 ) and scars following perforation ( p = 0.012 ) were identified as significant risk factors for graft failure .
immunological rejection ( n = 15 ) , surface problems like persistent epithelial defects ( n = 8) , graft infections ( n = 8) , postoperative glaucoma ( 10 ) , traumatic graft dehiscence ( n = 1 ) , and primary endothelial failure ( n = 1 ) were the causes of graft failure in our series .
of 181 patients observed , adequate data for survival analysis could be obtained in 170 patients .
eleven patients did not even come for the first follow - up ; therefore , these cases were excluded . since the event of interest in survival analysis is graft failure , for the remaining 170 cases , estimation of survival function was possible even though some of them did not complete one year of follow - up .
of 170 patients , graft failure was observed among 54 ( 31.76% ) patients during two - year follow - up period .
median survival of grafts in the cohort was 27 months ( 95% confidence interval [ ci ] : 20.47  33.52 ) .
65% of the grafts survived at 12 months , whereas 52.5% of the grafts survived at 24 months [ fig . 1 ] .
kaplan meier curve for graft failure graft survival did not differ between 2 gender groups ( male  23 months , females - 30 months , p = 0.119 ) and also between 2 recipient age groups ( < 60 years - 29 months , > 60 years - 27 months , p = 0.950 ) .
graft survival in good prognosis cases was 27 months ( 95% ci : 20.42 - 33.52 ) and in poor prognosis cases was 14 months ( 95% ci : 6.26 - 21.73 , p = 0.045 ) [ fig . 2 ] .
prognosis vs graft survival the prognosis of the case was determined on the basis of prior corneal vascularization , preexisting corneal perforation followed by scaring , history of herpes simplex keratitis ( hsk ) , and history of previous ipsilateral corneal graft .
the extent of vascularization of recipient bed correlates strongly with the graft survival , as demonstrated in the australian corneal graft registry ( acgr ) report so , we used quadrants of vascularization as one of the factors for grouping our cases into fair prognosis ( intermediate risk ) category and poor prognosis ( high risk ) category . in order to study the relation between individual risk factors like vascularization and graft survival , rather than low - risk vs high - risk group , our further analysis is designed accordingly . in eyes with more than two quadrants of vascularization (
n = 45 ) , and those with less than two quadrants of vascularization ( n = 48 ) , median graft survival was 18.55 months ( 95% ci : 15.6  21.4 ) .
in nonvascularized corneas ( n = 77 ) , median graft survival was 22.69 months ( 95% ci : 19.83 - 25.55 ) .
( n = 72 ) , graft survival was 17.96 months  1.43 ( 95% ci : 15.14  20.78 ) , whereas cases in which there was no perforation ( n = 98 ) , median graft survival was 22.56 months  1.403 ( 95% ci : 19.81 - 5.31 , p = 0.09 , borderline significant ) [ fig .
( n = 13 ) , graft survival was 16.9 months ( 95% ci : 11.56 - 22.27 ) , whereas in non - hsv keratitis ( n = 157 ) , graft survival was 20.95 months ( 95% ci : 18.72 , 23.73 , p = 0.544 ) [ fig .
5 ] . in previous failed grafts ( one or more grafts done elsewhere ) ( n = 21 ) , median graft survival was 14 months ( 95% ci : 5.55 - 22.44 months ) .
this was much lower than eyes with first - time grafts ( n = 149 ) in which median graft survival was 27 months ( 95% ci : 21.11  32.88 ) ; however , this difference was not statistically significant ( p = 0.207 ) [ fig . 6 ] . in eyes with postoperative glaucoma ,
the median graft survival was 18.35 months ( 95% ci : 13.94 - 22.76 ) as compared with eyes without postoperative glaucoma ( median , 21.59 months ; 95% ci : 19.30 - 23.88 ) .
graft survival in vascularized corneas graft survival in corneal perforations graft survival in hsv corneal scars graft survival in previous failed grafts postoperative glaucoma in our study , cases for which very good quality donor corneas ( n = 8) were used , had longer graft survivals ( 25.42 months ) as compared with other cases ( n = 147 , good quality graft ; n = 15 , fair quality grafts ) , but this difference was not statistically significant ( p = 0.41 ) [ fig
donor tissue quality vs graft survival in our series , we found that graft survival did not differ significantly in small size grafts ( 7.5  7 mm ) ( n = 66 ) , medium size ( 8  7.5 mm ) ( n = 85 ) , or large size grafts ( 8.5  8 mm ) ( n = 19 ) ( p = 0.549 ) [ fig .
graft size vs graft survival graft survival did not differ statistically ( p = 0.303 ) in different types of surgeries namely pk , ( n = 62 ) , pk triple ( n = 68 ) , and pk with additional surgery ( n = 40 ) [ fig . 10 ] .
additional surgeries included anterior vitrectomy ( 15 ) , pupilloplasty ( 4 ) , conjunctival limbal autografts ( 6 ) , and iol explants / exchanges ( 15 ) .
type of surgery vs graft survival in patients who followed up regularly ( n = 64 ) , medial graft survival time was 27 months ( 95% ci : 20.43 - 33.56 months ) as compared with irregular follow ups ( n = 106 ) in whom median graft survival time was 11 months ( 95% ci : 4.28 - 17.71 months , p = 0.001 ) [ fig .
follow - up vs graft survival table 3 summarizes the median survival time in months of corneal grafts and association between covariates and graft failure .
kaplan meier multivariate cox proportional hazard regression analysis was performed to evaluate the combined effect of ten risk factors [ table 4 ] . of these , vascularization ( p = 0.048 ) and scars following perforation ( p = 0.012 ) were identified as significant risk factors for graft failure .
immunological rejection ( n = 15 ) , surface problems like persistent epithelial defects ( n = 8) , graft infections ( n = 8) , postoperative glaucoma ( 10 ) , traumatic graft dehiscence ( n = 1 ) , and primary endothelial failure ( n = 1 ) were the causes of graft failure in our series .
corneal transplant surgery is the most commonly performed allograft and is said to be the most successful solid organ transplants , with short - term survival rates ( 1 year ) as high as 90% .
however , the long - term success rate diminishes to 73% at 5 years , 60% at 10 years , and 46% at 15 years as reported in acgr
. reports from various graft registries of the developed countries show the indications for surgery being mainly keratoconus , other corneal dystrophies , followed by aphakic and pseudophakic bullous keratopathies . however , the scenario in developing world is quite different .
firstly , the patient profile and indications for surgery differ . according to a study done in nepal , corneal scars following infectious keratitis ,
a study done in india to analyze survival rate of corneal transplants in a large series shows survival rates at 1 , 2 , and 5 years for first - time grafts to be 79.6% , 68.7% , and 46.5% , respectively .
they are different from the western studies essentially due to differences in patient profile , different indications for surgery , differences in methods of storage of corneas , and socioeconomic factors affecting healthcare provision .
our study shows much lower survival rates ( at one year - 65% , at 2 years - 52.5% ) . there is a variety of reasons for this . in our series , only one - third of our cases ( n = 65 , 35.91% ) were good prognosis cases like corneal dystrophies ( gelatinous droplet keratopathy , 1 ; granular dystrophy , 1 ; macular dystrophy , 1 ) , corneal degenerations ( 6 ) , and central / paracentral scars ( posttraumatic18 , postinfectious 38 ) .
most of our patients ( 64% ) are high - risk cases , which are at increased immunological risk of graft rejection due to factors like vascularized corneas , previous ipsilateral grafts , peripheral anterior synechiae , irregular anterior chamber , bullous keratopathies , herpetic eye disease with deep vascularization , etc .
secondly , most of our corneal collection is through voluntary eye donations by home calls , our donors being in the age group 60 years and above , with average quality of donor tissue and comparatively lower endothelial cell counts .
median survival in good prognosis cases ( corneal dystrophies and degenerations , corneal scars , etc ) was 27 months ( 95% ci : 20.42 - 33.52 ) , whereas in poor prognosis cases ( post - hsv corneal scars , previous failed grafts ) was 14 months ( 95% ci : 6.26 - 21.73 ) , the difference being statistically significant .
prasad eye institute , india , also shows higher survival for corneal dystrophies ( 56% , 5-year survival rate ) and lowest survival for previous failed grafts ( 21.2% , 5-year survival rate ) , although they have described results in terms of survival rates and not median survival time . in our analysis
, we found that extent of deep vascularization did not correlate statistically with graft survival , but the presence or absence of it did . in our series ,
the singapore corneal transplant study ( scts ) also found lower graft survival in vascularized corneas compared with nonvascularized ( p = 0.017 ) .
another study by price et al . too showed eyes with deep stromal vascularization three times more likely to experience rejection and failure ( rr : 2.7 , ci : 1.6 - 4.8 , p<0.01 ) . in our study , patients with previous corneal perforations had 45% more risk of failure ( multivariate analysis ) .
the sequel following perforation like vascularization , anterior synechiae with irregular anterior chamber , iridocorneal scar , and secondary glaucoma could have been responsible for lower survival rates .
scts has also shown corneal perforation as a very significant risk factor for graft failure ( hr - 3.16 , ci : 1.92 - 5.19 , p = 0.001 ) .
both these are well - established risk factors for graft failure , reported by various studies .
we found lower average survival time in post - hsv keratitis ( 16.9 months ) compared with non - hsv keratitis ( 20.95 months ) .
this agrees with other reports like the study from switzerland , in which at 5 years , cumulative probability of graft survival in hsk patients was 40.85% compared with 50.15% in non - hsk .
causes of graft failure in hsk patients were rejection ( 83.33% ) and recurrence of hsk ( 16.66% ) . in our study ,
graft survival was lower ( 14 months ) in previous failed grafts than that in first - time grafts ( 27 months ) .
prior graft failure as a risk factor in subsequent grafts is a well - known fact established by khodadoust , where rejection rate of 40% after first graft , 68% after second , and 80% after third graft was found .
we did not find statistically significant correlation between surgical factors like graft size , pk , and pk with associated procedure with graft survival .
this is perhaps due to the fact that like most other reputed centers , we follow well - established practice patterns of surgical and postoperative treatment
. we also found that patients who followed up regularly had better graft survival ( 27 months ) than those who did not follow up ( 11 months ) .
this once again emphasizes the need for good patient compliance and regular follow - up . in our series ,
major cause of graft failure was allograft rejection ( 34.88 ) , followed by surface problems ( 18.6% ) , graft infections ( 18.6% ) , and glaucoma ( 23.25% ) . a study done by dandona et al .
shows similar causes , e.g. , rejection ( 29.2% ) , increased intraocular pressure ( 16.9% ) , infections ( 15.4% ) , and surface problems ( 12.7% ) .
causes of non - improvement in vision were failed grafts ( 32 ) , preexisting amblyopia ( 2 ) , and preexisting optic disc pallor ( 2 ) .
we did not assess in details the effect of several donor tissue - related variables like death to in situ excision time , preservation time , age of the donor , hla matching or abo grouping of donor- recipient .
also , we have not taken into account effect of factors like preexisting glaucoma , inflammation , type of suturing , postoperative anterior or posterior uveitis , systemic immunosuppressant , and rejection episodes .
reversible graft rejection is an important risk factor , responsible for about one - third of corneal graft failures in acgr .
also , our study shows survival rates for a relatively short period , i.e. , 1 to 3 years .
we are in a process of collecting and analyzing data over longer periods like 5 to 7 years .
nearly one - third to half of our patients have been lost to follow - up ( n = 69 ) causing several limitations to analysis .
still to conclude , short - term success and survival of corneal grafts in this part of the developing world is reasonably good . our study has validated the normally accepted facts regarding outcome and survival of corneal grafts .
further improvements in eye banking facilities , adopting hospital cornea retrieval programme to procure young donor corneas , and better patient counseling to ensure good follow - up are needed to improve long - term survival of corneal grafts .
 aim : to study the indications , risk factors , postoperative course , and long - term survival of corneal transplants done for optical purposes.design:retrospective case series.materials and methods : data were obtained by reviewing the records of 181 patients operated at our institute ( h.v . 
 desai eye hospital ) between october 2005 and october 2007 for optical penetrating keratoplasty . 
 patients with less than one year of follow up , pediatric cases , therapeutic , tectonic , and lamellar keratoplasties were excluded . 
 kaplan meier survival analysis was used to calculate median survival time of grafts and to see correlation between nine variables viz . 
 age , gender , corneal vascularization , previous failed grafts , previous herpes simplex keratitis , post - perforation corneal scars , donor tissue quality , graft size , type of surgery and follow - up . 
 these variables were also used for univariate and multivariate analysis using cox proportional hazard regression modeling.results:median survival of the cohort was 27 months ( 95% confidence interval : 20.47 - 33.52 ) . 
 one- and two - year survival rates were 65% and 52.5% , respectively . 
 median survival was significantly lower in poor prognosis cases ( 14 months ) than good prognosis cases ( 27 months , p = 0.0405 ) . 
 graft survival was lower in vascularized corneas ( 18.55 months , p = 0.030 ) and in post - perforation corneal scars ( 17.96 months , p = 0.09 , borderline significance ) . 
 multivariate analysis showed that the same factors were predictive of graft failure.conclusion:long-term survival of grafts at our center is different from centers in western world . 
 more high - risk cases , paucity of excellent quality donor corneas , and differences in patient profile could be the contributory factors . 
Materials and Methods
Results
Kaplan meier univariate analysis
Discussion