Patricia Durán Ospina

*Fundación Universitaria del Área Andina Seccional Pereira Colombia*

#### **1. Introduction**

Keratoplasty is the medical term that refers to a cornea transplant. There are some differences between the definitions of keratoplasty, commonly it is mentioned for corneal transplant, Lamellar Keratoplasty, which is a partial thickness corneal grafting and penetrating keratoplasty: is a full-thickness corneal grafting. The indications for keratoplasty include: optical (to improve visual acuity by replacing the opaque host tissue by a healthy donor or pesudophakic bullous keratopathy), tectonic (in patients with stromal thinning and descemetoceles, to preserves corneal anatomy ant integrity), therapeutic (removal of inflamed corneal tissue refractive to treatment by antibiotics or antiviral drugs) or cosmetic (in patients with corneal scars giving a whitish opaque hue to the cornea.

The most frequent causes of corneal alterations leading to keratoplasty are keratoconus, bacterial infections, poor hygienic contact lens wear (Buehler et al. 1992, Chalupa, 1987, Holden, 2003) or trauma. Among microbial infections, bacterial infections are the most frequent and are mainly caused by *Staphylococcus sp., Streptococcus sp. or Pseudomona sp.*

Some side effects of keratoplasty can be infection (keratitis on the new transplanted cornea or endophthalmitis), transplant rejection, vision fluctuation, glaucoma and bleeding, among others less reported. Infection is one of the most frequent complications after keratoplasty, which can cause endophthalmitis. Infection after keratoplasty, can result from inapropiate healing or like a complication during the transplant (Confino and Brown, 1985 and Dana, 1995). even though the area around the eye is completely sterilized the day of the surgery and the face is covered with sterile drapes. Despite these actions to keep the surgical area clean, infections still may occur.

On the other hand, transplant rejection is one of the hardest complications after keratoplasty. It occurs when the body rejects the new cornea. But it can occur from days to several years after surgery. Symptoms that show that the immunological system has rejected the cornea may be redness of the eye, an extreme sensitivity to light and pain, autoimmune diseases, infiltrates and also unknown causes. Signs of rejection may occur anywhere from one month to several years after the transplant surgery. On these cases, keratoplasty can be repeated when the transplant is rejected and oral immunosupresor drugs must be taken for long time to reduce the rejection. Some authors are reported also vision fluctuation after keratoplasty, frequent symptoms are poor vision and fluctuations for up to several months or years. Not until the vision has reached a constant and the sutures have been removed can the individual be given a prescription for eyeglasses or special contact lenses.

The Complications After Keratoplasty 103

of this pathology it is important to make routine microbial tests: (culture of microorganisms, mycobacteria, polymer chain reaction (PCR), mycoplasm, Chlamydia, simplex virus, adenovirus and endotoxins (limulus amebiocyte lysata, QCL 1000, Cambrex Bio Science). Some factors to take into account to protect the cornea in these surgeries are prophylactic antibiotic treatment, asepsis eye with an appropriate antiseptic prior to surgery, postoperative antibiotic treatment, age, nutrition and immunosuppressant of the patient and to be taken considered minimizing the risk of postsurgical infection. Before this surgical procedure should be performed before the control protocol for signs or symptoms of eye infection and make an effective and timely microbiologic diagnosis. In the case of mixed microbial infections reported leading to keratoplasty (bacteria-bacteria or bacteria-fungi) (Garcia et al.2004, Delgado et al.2008), it should be clear which is the microorganism more dangerous to invade cornea (fungus or bacteria) to inhibit it with the indicated treatment (antimycotic or antibiotic agent, respectively) , knowing the physiopathology of the infection, the mechanisms of adhesion (biofilm formed for bacteria or hyphaes for fungus) and reflect on the use of corticosteroids in ocular infection, because it which may exacerbate the corneal infection in most cases with corneal compromise. Asepsis previous eye surgery, irrigating with povidone-iodine a day before surgery, has proved a good choice to prevent

Corneal complications due to other ophthalmic surgeries like post intraocular implants relation have been associated with edema. It occurs for many reasons, but it is often a sequel of intraocular surgery, called either pseudophakic bullous keratopathy (PBK) or aphakic bullous keratopathy (ABK). Knowledge of the structure of the cornea and the proper functioning of its layers is fundamental to understanding corneal edema. Authors suggest that the endothelium becomes increasingly unable to act as a pump to deturgesce the cornea, it causes the stroma begins to swell, especially in the central cornea. As the stroma swells, the cornea thickens and folds are seen in the Descemet membrane. The edema may fluctuate in response to changing intraocular pressure with higher pressures leading to more edema. At this point, maintenance of intraocular pressure at a low level is important. The combination of variable endothelial function and variable intraocular pressure

This chapter is a description of microbial complications in keratoplasty, to understand the physiology and behavior of these microorganisms in the surgical process, the relationship with the ocular immune system at the time of surgery, knowing the clinical findings to identify whether a bacterial infection, viral or fungal infection may be present. Another factor to evaluate the postoperative course of keratoplasty is the type of antibiotic used after keratoplasty and should be evaluated according to clinical evidence, since in many cases is not time for microbiological culture fungal or bacterial infection alone is assessed, but fungi

Microbial complications post-keratoplasty may even become worse on endophthalmitis and in the worst cases enucleating of some inevitable cases. In vitro studies, it have shown that the anatomy of corneal tissue which allows the invasion of microorganisms in and its biochemical composition. The corneal stroma lamellar structure composed of collagen fibrils which contribute to corneal transparency, being invaded by microorganisms allows rapid entry stromal inflammatory cells, predisposing to ulcers. Crystalline keratopathy caused by *Streptococcus sp*. should not confuse with a fungal infection because it form a crystalline

infection after the keratoplasty (Nash et al. 1991).

determines the extent of corneal edema (Aquavella et al, 2010).

attack the corneal stroma, being more aggressive with corneal tissues:

forms similar to mycotic hyphaes. (Butler et al.2001).

Other reports refer to glaucoma like a potential complication after keratoplasty. Glaucoma is a buildup of pressure in the eye that can cause a complete loss of vision. Keratoplasty increases the chances of pressure buildup during the surgical procedure that may lead to glaucoma for metabolism changes on the stroma or perhaps can be caused for immunological reactions or metabolic associations. It depends of the clinical history of each patient, not all cases are the same, by this reason must be studied independently. Additionally, may appear bleeding and pain after keratoplasty, sometimes the blood vessels may leak, which would result in bleeding from the eyes. In these cases, sitting upright will encourage the blood to settle. Pain after the keratoplasty is a common side effect oftentimes due to dry eyes. In theory the dry eye contribute with corneal infection, probably due to the opportunistic microbes, which invade the tissue, also is the same with the use of contact lenses for long periods due to hypoxia (low oxygen) (Mertz G. 1980) and to hypercapny (increase of carbon dioxide CO2). Patients usually feel pain and discomfort when they move the eye at all for weeks after surgery.

Ocular infection occurs mostly in immunosuppressed patients, prior diabetes mellitus, hypertension, hypoadrenalism, taking oral corticosteroids, atopic dermatitis; prolonged use and low hygienic conditions with contact lenses (soft lenses are more frequent than RGP contact lenses) , opportunistic microorganisms which interfered with normal flora, dry eye and a low percentage for contamination of the surgical team. The etiology of keratoplasty in cases of microbial infection has been reported by several authors, as well as the findings on postoperative keratoplasty, one of the main causes is keratoconus and previous corneal graft rejection. The most common microbiological findings correspond to bacteria such as *Staphylococcus sp., Pseudomonas sp., Pneumococcus sp. Serratia marcescens, Streptococcus pneumoniae, Streptococcus viridians, Bacillus* sp., *Corynebacterium sp*. primarily and other microorganisms such as fungi (*Candida sp. Candida glabrata, Aspergillus sp., Fusarium* sp.), among the viruses that are mostly found associated with keratoplasty are the *herpes simple*.

In the reports of eye infection as a complication after keratoplasty, the finding of organisms corresponds in most cases to opportunistic bacteria of the normal ocular flora. In a prospective study conducted in 2004 by a team of researchers in Japan (Wakimasu et al. 2004). They found in a retrospective study among 753 eyes with microbial keratitis after keratoplasty, 14 had bacterial and 13 fungal infections. The time intervals between transplantation and the onset of infection averaged were seven months on average for bacteria and 24 for fungus. In many cases unexpected occasions are to be studied independently and allow further studies regarding the appropriate surgical protocol and the use of antibiotic and steroid therapy to prevent such cases in future.

Even reports of mixed infections are: bacteria-bacteria, fungus or bacteria. Associated with these findings should be taken into account the presence of bacterial endotoxins are another complication of keratoplasty of microbial origin, producing toxic anterior segment syndrome (TASS), which has been attributed to the use of intracamerular antibiotics, reusable cannulas, cleaning the instrumental use of detergents or non-ionized water, among others (Maier et al. 2010). Moreover, the time of onset of infection can vary from weeks to years of development after transplantation. The associated risks are contaminated sutures, persistent epithelial defects. The clinical appearance of TASS is typically characterized by intense early postoperative inflammation of the anterior ocular segment. Sometimes it can be accompanied by fibrin formation, corneal edema, without periocular pain. For diagnosis

Other reports refer to glaucoma like a potential complication after keratoplasty. Glaucoma is a buildup of pressure in the eye that can cause a complete loss of vision. Keratoplasty increases the chances of pressure buildup during the surgical procedure that may lead to glaucoma for metabolism changes on the stroma or perhaps can be caused for immunological reactions or metabolic associations. It depends of the clinical history of each patient, not all cases are the same, by this reason must be studied independently. Additionally, may appear bleeding and pain after keratoplasty, sometimes the blood vessels may leak, which would result in bleeding from the eyes. In these cases, sitting upright will encourage the blood to settle. Pain after the keratoplasty is a common side effect oftentimes due to dry eyes. In theory the dry eye contribute with corneal infection, probably due to the opportunistic microbes, which invade the tissue, also is the same with the use of contact lenses for long periods due to hypoxia (low oxygen) (Mertz G. 1980) and to hypercapny (increase of carbon dioxide CO2). Patients usually feel pain and discomfort when they move

Ocular infection occurs mostly in immunosuppressed patients, prior diabetes mellitus, hypertension, hypoadrenalism, taking oral corticosteroids, atopic dermatitis; prolonged use and low hygienic conditions with contact lenses (soft lenses are more frequent than RGP contact lenses) , opportunistic microorganisms which interfered with normal flora, dry eye and a low percentage for contamination of the surgical team. The etiology of keratoplasty in cases of microbial infection has been reported by several authors, as well as the findings on postoperative keratoplasty, one of the main causes is keratoconus and previous corneal graft rejection. The most common microbiological findings correspond to bacteria such as *Staphylococcus sp., Pseudomonas sp., Pneumococcus sp. Serratia marcescens, Streptococcus pneumoniae, Streptococcus viridians, Bacillus* sp., *Corynebacterium sp*. primarily and other microorganisms such as fungi (*Candida sp. Candida glabrata, Aspergillus sp., Fusarium* sp.), among the viruses that are mostly found associated with keratoplasty are

In the reports of eye infection as a complication after keratoplasty, the finding of organisms corresponds in most cases to opportunistic bacteria of the normal ocular flora. In a prospective study conducted in 2004 by a team of researchers in Japan (Wakimasu et al. 2004). They found in a retrospective study among 753 eyes with microbial keratitis after keratoplasty, 14 had bacterial and 13 fungal infections. The time intervals between transplantation and the onset of infection averaged were seven months on average for bacteria and 24 for fungus. In many cases unexpected occasions are to be studied independently and allow further studies regarding the appropriate surgical protocol and the

Even reports of mixed infections are: bacteria-bacteria, fungus or bacteria. Associated with these findings should be taken into account the presence of bacterial endotoxins are another complication of keratoplasty of microbial origin, producing toxic anterior segment syndrome (TASS), which has been attributed to the use of intracamerular antibiotics, reusable cannulas, cleaning the instrumental use of detergents or non-ionized water, among others (Maier et al. 2010). Moreover, the time of onset of infection can vary from weeks to years of development after transplantation. The associated risks are contaminated sutures, persistent epithelial defects. The clinical appearance of TASS is typically characterized by intense early postoperative inflammation of the anterior ocular segment. Sometimes it can be accompanied by fibrin formation, corneal edema, without periocular pain. For diagnosis

use of antibiotic and steroid therapy to prevent such cases in future.

the eye at all for weeks after surgery.

the *herpes simple*.

of this pathology it is important to make routine microbial tests: (culture of microorganisms, mycobacteria, polymer chain reaction (PCR), mycoplasm, Chlamydia, simplex virus, adenovirus and endotoxins (limulus amebiocyte lysata, QCL 1000, Cambrex Bio Science).

Some factors to take into account to protect the cornea in these surgeries are prophylactic antibiotic treatment, asepsis eye with an appropriate antiseptic prior to surgery, postoperative antibiotic treatment, age, nutrition and immunosuppressant of the patient and to be taken considered minimizing the risk of postsurgical infection. Before this surgical procedure should be performed before the control protocol for signs or symptoms of eye infection and make an effective and timely microbiologic diagnosis. In the case of mixed microbial infections reported leading to keratoplasty (bacteria-bacteria or bacteria-fungi) (Garcia et al.2004, Delgado et al.2008), it should be clear which is the microorganism more dangerous to invade cornea (fungus or bacteria) to inhibit it with the indicated treatment (antimycotic or antibiotic agent, respectively) , knowing the physiopathology of the infection, the mechanisms of adhesion (biofilm formed for bacteria or hyphaes for fungus) and reflect on the use of corticosteroids in ocular infection, because it which may exacerbate the corneal infection in most cases with corneal compromise. Asepsis previous eye surgery, irrigating with povidone-iodine a day before surgery, has proved a good choice to prevent infection after the keratoplasty (Nash et al. 1991).

Corneal complications due to other ophthalmic surgeries like post intraocular implants relation have been associated with edema. It occurs for many reasons, but it is often a sequel of intraocular surgery, called either pseudophakic bullous keratopathy (PBK) or aphakic bullous keratopathy (ABK). Knowledge of the structure of the cornea and the proper functioning of its layers is fundamental to understanding corneal edema. Authors suggest that the endothelium becomes increasingly unable to act as a pump to deturgesce the cornea, it causes the stroma begins to swell, especially in the central cornea. As the stroma swells, the cornea thickens and folds are seen in the Descemet membrane. The edema may fluctuate in response to changing intraocular pressure with higher pressures leading to more edema. At this point, maintenance of intraocular pressure at a low level is important. The combination of variable endothelial function and variable intraocular pressure determines the extent of corneal edema (Aquavella et al, 2010).

This chapter is a description of microbial complications in keratoplasty, to understand the physiology and behavior of these microorganisms in the surgical process, the relationship with the ocular immune system at the time of surgery, knowing the clinical findings to identify whether a bacterial infection, viral or fungal infection may be present. Another factor to evaluate the postoperative course of keratoplasty is the type of antibiotic used after keratoplasty and should be evaluated according to clinical evidence, since in many cases is not time for microbiological culture fungal or bacterial infection alone is assessed, but fungi attack the corneal stroma, being more aggressive with corneal tissues:

Microbial complications post-keratoplasty may even become worse on endophthalmitis and in the worst cases enucleating of some inevitable cases. In vitro studies, it have shown that the anatomy of corneal tissue which allows the invasion of microorganisms in and its biochemical composition. The corneal stroma lamellar structure composed of collagen fibrils which contribute to corneal transparency, being invaded by microorganisms allows rapid entry stromal inflammatory cells, predisposing to ulcers. Crystalline keratopathy caused by *Streptococcus sp*. should not confuse with a fungal infection because it form a crystalline forms similar to mycotic hyphaes. (Butler et al.2001).

The Complications After Keratoplasty 105

of tear that low lubrication caused by widespread use is a factor that should be taken into account users contact lenses (Kwong, 2007), because the tear is carrier lysozyme, lactoferrin, and immunoglobulins -lysine that being dehydrated lens facilitates

There are a lot of reason for make microbial culture collection in all protocols to identify the type of microbial keratitis pre or post keratoplasty: Signs are similar in bacterial keratitis, exist mixed infections which required different treatments, there are several signs can help to make the differential diagnosis prior to the results of the microbiological findings, some of these are:

> Feathery borders or hyphate edges

white or yellowish-white, and the base of the ulcer is often filled with soft, creamy, raised exudates, dematiaceousfungi: brown or black pigmentation on the surface of the ulcer.

Vegetal origin foreign body contamination, dirty case lenses storage, immunosupression.

*Aspergillus sp, Fusarium sp., Candida sp.* 

(Muzaliha et al.,2010)

Table 1. Microbes finding on clinical pearls of keratitis complications associated with corneal

No No No Immunological ring

and leathery

**MYCOTIC KERATITIS HERPES**

**KERATITIS**

lession)

Dendritic ulcers

Immunosupression

No No

**ACANTHAMOEBA KERATITIS** 

Yes

White White or grey

Regular

Contaminated water, dirty contact

lens case contaminated

*Herpes simple Acanthamoeba sp.* 

*(* McCulley,2000) (Varga et al.1993)

at the limbus

molecular adhesion of *P. aeruginosa* (Zhu et al. 2002).

**SIGNS BACTERIAL**

Lession borders

Color infiltrates

Frequent Causes

Microorganisms

Stromal immunologica l ring

**KERATITIS**

**3.1 Differential diagnosis between keratitis caused by microbes** 

Hyperemy Yes Yes Yes Yes Satellite lesion No Yes No No Pain Yes Yes Yes (Active

Regular Diffused and irregulars,

White, cream, yellow infiltrates appear grayish-

Hypopyon Yes or no which appears dry, rough,

corneal foreign body, contact with nonsterile water, bullous keratopathy, neurotrophic keratopathy, herpes simplex keratitis, radial keratotomy, swimming and scuba diving, basement membrane dystrophy, contact lens wear and bacterial keratitis

*Staphylococcus sp., Streptococcus sp., Pseudomona sp.Mycobacterium sp.* 

infections after keratoplasty and common treatment.
