Penetrating keratoplasty (PK) has been the procedure used almost universally for the treatment of corneal pathologies that irreversibly affect vision, up to the development and popularization of anterior lamellar and endothelial lamellar keratoplasty techniques in the last decade. Until the end of the last century, laminar (anterior) keratoplasty was used almost exclusively – except in some centers – in relatively rare reconstructive situations. Therefore, the distribution of the indications of the PK reflected roughly the pathologies susceptible to corneal transplantation in a certain part of the world.

FUNCTIONAL CLASSIFICATION OF INDICATIONS FOR KERATOPLASTY

The most usual way to organize the PK indications follows the functional classification (see chapter 1.2), that is, according to the function of the cornea that they restore: a) recover transparency as in leucomas, dystrophies and degenerations, or irreversible edema (optical purpose); b) recover the quality in the formation of the images by correcting the irregular astigmatism, as in keratoconus and other ectasias (refractive purpose); c) reconstruct the corneal ocular wall before a loss of substance or perforation (tectonic purpose), and d) defend the eye from an infection that does not respond to medical treatment (defensive purpose, anti-infective, "therapeutic" or "hot"). As we already mentioned, in practice many cases participate in more than one of these purposes, but this does not detract from the classification scheme.

THE SERIES OF BARCELONA 1948-1995

In 1996 we presented a study on PK performed at the Barraquer Ophthalmology Center (COB) in Barcelona, between 1948 and 1995¹. The distribution of the indications of the 5,369 cases that we were able to review is summarized in Figure 1. It highlights keratoconus and other ectasias, with almost 27%, followed by the leucomas after herpetic keratitis (14%) and the re-grafts (12.4%). If we group all the leucomas except those traumatic, 24% is reached (including 2.3% of trachoma). The group of dystrophies and degenerations represents 10.3% (5.8% of the stroma and 4.5% of the endothelium). Edematous keratopathy (OK) or vesicular (bullous) aphakic or pseudophakic barely exceeded 8%. This distribution contrasts with other series published in the literature of the same period² and is completed with both 6.6% for "hot" and trauma PK’s, plus 4.2% after burns, and 0.6% early failures.

HISTORICAL EVOLUTION OF INDICATIONS

The progression of edematous keratopathy

The change in the indications for PK was the reason for an increasing number of publications from the 1970s³, in particular due to the clear progression of OK (aphakic or pseudophakic), which quickly became the main cause of PK in several series in North America. If until the 1960s the OK represented less than 1%, in the following decade they rose to 10%, reached 20% at the end of the '70s and reached 37% by the end of the 1980s⁴. This phenomenon was described by George O. Waring III as "the epidemic of 50 years of pseudophakic corneal oedema"⁵, which would present three epidemic waves of increasing amplitude, linked to the development of the different types of intraocular lens (IOL): a first one with the pioneers of the anterior chamber (AC) in the 50s, the second one with the IOL of iridian support in the '70s (Figure 2), and the third one with the AC-closed handle-angular support IOL in the '80s. Apparently, that would have been the price to pay for the advance that the IOLs supposed.

The progression of OK as an indication of PK at that time was also found in series in the United Kingdom⁶ and in Australia⁷, which in both cases reached 25% while previous studies gave values around 10%. However, some series find values as low as 1.7%⁸, and there are notable differences according to countries. The series of the Hôtel-Dieu de Paris found OK as the cause in 9.5% of 2,962 PK between 1980 and 1991, although it went from 7.2% in 1980-87 to 15.3% in 1988-91⁹. A comparative study between PK from Brazil and Canada found OK as an indication in respectively 2.6% and 57.1% of cases¹⁰.

Evolution of the main indications in our series

If we break down our series by epochs, the OK represented 1.7% in 1948-70; 3-4% between 1971 and 1985; 10% in 1986-90; and 16% in 1991-95. In the case of keratoconus, the percentages remain stable between 27% and 32%, and although they dropped to 22% in the 1991-95 period, they later recovered. The post-herpes leucomas had reached 24% in 1976-80, but dropped to 7% from 1986 onwards, which may reflect the improvement in medical treatment. As expected, the percentage of re-grafts increased progressively from 6% before 1975 to 18% in 1991-95 (Figure 3). Another Spanish series of 1980-94¹¹ finds the re-graft as the 1^st cause (19.3%), followed by the post-herpes leucomas (18.3%). The OK (aphakic and pseudophakic) represented 11.6% of the total, although the pseudophakic OK, non-existent in the period 1980-85, reached 20.4% in 1989-91.

As Waring predicted, OK's "epidemic" began to subside at the end of the century, with the generalization of posterior chamber IOLs and improvements in phacoemulsification technology and learning. However, until its progressive substitution by endothelial keratoplasty, OK has remained one of the main indications of PK (see next chapter).

Evolution of the causes of edematous keratopathy

Regarding the causes of OK that required PK in our series, the different distribution according to the period draws attention (Figure 4). Until 1984, more than 2/3 of the cases were aphakic and 15.6% had AC phakic IOL (for myopia), with only 2.6% of AC pseudophakia. In the period 1985-95, aphakic patients are a little more than 1/3, phakic IOLs have fallen to 3.9%, and pseudophakia accounts for 48%. However, in this last group, the IOLs of AC were not much more than half (27.9%) and still 20.1% of the edemas were with posterior chamber IOL.

Progression of primary failure

Finally, a minor but perhaps significant aspect has been the evolution of the primary graft failures in this series. Up to the year 1985 there were 6 cases (0.23%); in the period 1986-90 there were 7 (0.5%), and 21 in 1991-95 (1.6%). These are modest figures, but the progression seems obvious, more than 5 times. This contrasts – especially visible in a cumulative graph "by levels" (Figure 5) – with the relative stability of keratoconus and the less marked rise of OK. Although the primary failures can be due to multiple causes, until 1990 all the PKs in the COB used refrigerated fresh whole eye globes and thereafter the preservation of the separated corneoscleral cap in cold medium (Optisol®) at 4 °C was introduced.

The recent surge in the different modalities of lamellar keratoplasty, both anterior (ALK) and posterior or endothelial (EK), has put an end to the hegemony of penetrating keratoplasty (PK) in corneal transplants. However, PK remains the most common type of transplant in the world¹, and there are several situations in which it may be preferable to any lamellar modality, either because the pathology affects all the corneal layers or by other factors that concur in a determined patient. Therefore, the decision on which technique to apply, should only be taken after a complete evaluation of each case.

CORNEAL TRANSPLANTS IN THE WORLD

The most recent global data correspond to 2012, due to a systematic study of the literature and surveys of corneal surgeons and eye banks from 148 countries¹. A total of 184,576 transplants from 283,530 corneas provided by 742 eye banks from 82 countries were identified. Given that the cornea is the 3^rd most frequent cause of blindness in the world, with 10 million people with bilateral corneal blindness, these figures indicate that only 1 cornea is available for every 70 patients who need it. It is estimated that 53% of the world population does not have access to corneal transplants.

The rate of corneal transplants per million population (pmp) was highest in the USA (199), followed by Lebanon (122) and Canada (117). In Spain it was 76 pmp and the median of 116 countries was 19 pmp. The most frequent indication was Fuchs' dystrophy (39%), followed by keratoconus (27%) and the sequelae of infectious keratitis (20%)¹.

RECENT EVOLUTION OF THE INDICATIONS

According to data from the Catalan Transplantation Organization (OCATT)², in the past decade the first cause of corneal transplantation in Catalonia was postoperative corneal edema (23.5% and 22.3% of the cases with reported diagnosis, respectively in 2007 and 2015), followed by re-transplantation (16.1% and 12.9%), keratoconus and other ectasias in 3rd place (13.0% and 14.3%), surpassed as of 2012 by Fuchs’ and other endothelial dystrophies (8.0% increased to 16.6% in 2015) (Table 1).

COMPARISON BETWEEN PENETRATING KERATOPLASTY AND OTHER MODALITIES

The statistics of the Eye Bank Association of America (EBAA)³ on the domestic use of corneal tissue in the period 2005-2015 reveal the progressive reduction of PK, which corresponds to an increase in EK, while the anterior lamellar modalities keep being a minority (Figure 1).

In the period 2011-2015, the total number of corneal transplants from American eye banks (EBAA) – be they domestic or international use – increased from 67,590 to 79,304 (17.3%). Of these, PKs were 53.5% in 2011 and 49.9% in 2015. The EK increased from 34.5% to 38.7%, while the ALK just went from 2.6% to 2.7% in that same period³. According to data from the OCATT in 2015, of the total of 986 keratoplasties reported, 583 (59.1%) were PK, 135 (13.7%) ALK, and 191 (26.9%) EK². In the United Kingdom, the trends were similar. The PK rate had increased from 7 pmp in 1971 to 39 pmp in 1992 and then fell to 31 pmp in 2006. In the same period, the lamellar ones went from 1 to 9 pmp. The annual PK total number decreased from 1,901 in 1999/00 to 1,473 in 2008/09 (22.5%), while that of ALK increased from 91 to 327 per year and that of EK from 2 to 569 per year (Figure 2)⁴.

INDICATIONS ACCORDING TO THE MODALITY OF KERATOPLASTY

According to the OCATT in 2015, of 22.3% of postoperative edemas that required transplantation, 58.6% were still PK, 31.4% DSAEK and 8.2% DMEK. Among the endothelial dystrophies (16.6%), the EK (76.2%) far outnumber the PK (19.5%). Keratoconus and other ectasias (14.3%) are divided between PK (43.3%) and DALK (53.2%). Of the re-transplants (12.9%), 75.6% were PK. Even breaking down the failures of endothelial cause (7.9%), only 29.5% of them were subject to EK (Table 2)².

RECENT INDICATIONS OF PENETRATING KERATOPLASTY

The indications of PK are changing due to the role of the lamellar techniques. However, this effect has been noticed especially since the last decade. During the period 2001-2006, the indications of PK in Centro de Oftalmología Barraquer did not vary substantially from those of the previous period (see chapter 3.1.1). In fact, keratoconus and other ectasias increased to 38% of 966 PK, followed by re-grafts (28%) and non-traumatic leucomas (20%), with edema due to endothelial failure – whether due to dystrophy or postoperative – (19 %) in fourth place.

According to the EBAA, the most frequent indication of PK remains keratoconus, although it goes down from 16.8% to 14.8%, respectively in 2013 and 2015. Re-transplants follow (11.5% and 10.8% in the same years), corneal edema after cataract surgery (9.2% and 7.3%), Fuchs' dystrophy (3.3% and 3.1%) and other dystrophies and degenerations (4.9% and 3.1%), although there are 32.2% and 41.4% of cases classified as "unknown, not informed or not specified"³.

In the OCATT data in 2015, however, the most frequent indication for PK was postoperative edema (22.1%) followed by re-transplants (16.5%), with keratoconus and ectasias in only 10.5% (table 1). The latter is possibly due to the greater application of DALK in our country today, as well as the conservative treatments of keratoconus such as crosslinking or intracorneal ring implants. Something similar happens in other regions of Europe such as the Netherlands, where there has been a reduction in the annual number of transplants for keratoconus, which were 106 in 2005, a maximum of 128 in 2008, and 86 in 2014. Of these, PK, which represented 81% in 2005, fell to 71% in 2014, while ALK went from 18% to 26.7% (Figure 3)⁵.

SELECTION AND PREPARATION OF THE PATIENT FOR PENETRATING KERATOPLASTY

The decision to guide a patient into having a PK supposes first of all the pathologies that affect all the layers of the cornea, both the stroma and the endothelium. This includes – from more to less clearly defined:

a) Perforated eyes as well as after penetrating traumatisms – although a DALK can be attempted in the descemetocele (see chapter 5.8.2) –;

b) Non-controllable corneal infections with medical treatment in which there is no guarantee that the Descemet’s membrane (DM) and the endothelium are not affected – this includes infections at the interphase of a DALK or DSAEK (see chapters 5.6.4 and 6.9.6);

c) Chronic endothelial failure with established stromal opacity, neither reversible nor dissectible, or with high risk of vascularization of a lamellar interphase. More frequently in old failed PK or a very advanced postoperative edematous keratopathy;

d) Keratoconus or other ectasias with a history of rupture of the DM (hydrops), or in extreme cases – great ectasia and thinning, keratoglobus, etc. – together with the need for good vision, something that a predescemetic DALK does not guarantee, while a descemetic one is technically very difficult (see chapter 5.3);

e) Stromal dystrophies that affect deep layers of the cornea, especially the macular type (Groenouw II) and some forms of the lattice (Biber-Haab-Dimmer) or others that tend to recur rapidly in a lamellar interphase. The state of the endothelium should always be checked, since a stromal opacity – even anterior like a band degeneration – may be due to an endothelial dysfunction, e.g., a posterior polymorphic dystrophy.

All the above are more or less relative criteria and successes have been described with lamellar techniques in some cases of that list. The final recommendation must be decided on a personalized basis, after evaluating the patient's medical history, their needs and expectations, previous surgeries in that eye or the other, associated pathologies, etc. and all the examination data. This should include, in addition to the functional examination, the bio microscopy of the anterior segment and the retina examination (where possible), and image tests that give us an idea of ​​the dimensions, shape and thickness of the cornea. The first is important in order to predict how the postoperative curvature will be and decide on the ratio of the graft-window sizes to be used – especially in combined procedures with cataract and IOL –. The second, in order to program the depth of trepanation with less risk of intraocular damage. Routine biometry is recommended, even in cases without planned crystalline lens surgery; for example, in keratoconus, myopia can be corneal in the presence of an axial hyperopic eye globe.

In opaque and/or irregular corneas, the spectral optical coherence tomography (OCT) is more robust than other technologies to obtain topographic and pachymetric maps (see chapter 1.5), in addition to visualizing possible problems in the anterior chamber, such as synechiae, etc. With the confocal microscope, the endothelium is sometimes observed in the presence of stromal opacities that prevent the use of the specular microscope. If there is edema, remember the usefulness of a few drops of glycerin to reduce it temporarily. Although the retina examination can be difficult, ultrasound is essential to at least rule out macroscopic lesions and OCT sometimes achieves images of the macula through non-transparent corneas. In case of doubt about the indication for poor vision or if the best eye should be chosen, the electrophysiological tests will be useful, without forgetting the most elementary ones such as the luminous location and the entoptic phenomena – applying a flashlight (on or off) on the sclera –.

Another fundamental aspect of the preparation of the patient for PK – or any type of keratoplasty – is the study and eventual treatment of the ocular surface (see chapter 1.7), since any significant alteration of the same can lead to failure if it is not corrected or stabilized before surgery. If there are corneal neovessels, it is advisable to eliminate them if possible, either previously by means of a combination of coagulation and anti-proliferative agents or in the immediate preoperative period.