Fig. 16.1
Post-penetrating keratoplasty graft infection with endophthalmitis
Fig. 16.2
Post-DSEK endophthalmitis. (a) A case of pseudophakic corneal oedema that received DSEK. (b) Post-DSEK acute endophthalmitis with infiltrates in donor lenticule and anterior chamber. (c) Gram-negative coccobacilli (arrows) seen in smears (Gram stain, 100×). (d) Blood agar showed white mucoid colonies (centre) of Klebsiella pneumoniae (Courtesy: Shilpa Das, MD)
Differential Diagnosis
A number of conditions mimic endophthalmitis. An acute episode of graft rejection is the most common condition confused with a case of endophthalmitis. A case of acute rejection would present with sudden graft oedema, with reduction of vision, epithelial and endothelial rejection line, the presence of keratic precipitates and possible raised intraocular pressure. The absence of infiltrates on the donor cornea, presence of red reflex and rapid resolution in response to steroid differentiate a graft rejection from endophthalmitis.
A recurrent corneal herpetic infection is another entity which can be confused with post-penetrating keratoplasty endophthalmitis. A history of previous episodes of redness and pain, affliction of both donor and host cornea and prompt response to antiviral therapy differentiate a herpetic corneal infection from post-keratoplasty endophthalmitis.
Investigations
Every clinically diagnosed case of endophthalmitis should be confirmed by culturing the organisms from the intraocular samples. The area of the donor tissue with infiltrates should be scrapped for microscopy and culture. At least two smears are prepared, one for Gram staining and the other for potassium hydroxide (KOH) wet mount. Further, the scrapping should be directly inoculated into the culture media, and sensitivity of the organism to the antibiotics should be obtained. The corneal samples are routinely inoculated onto blood agar plate and Sabouraud’s dextrose agar, when fungus is suspected. If a suture abscess or infected suture tract is present, the removed suture must be cultured. B-scan ultrasonography should be done to look for mild to moderate spikes in vitreous cavity suggestive of exudates. The most important samples to be cultured are aspirates from the aqueous and vitreous cavity. Vitreous biopsy taken and cultured in such cases may serve as a useful guide to the treatment.
Prevention
Since the treatment outcome in endophthalmitis after penetrating keratoplasty is poor, prevention of such infection is more important. The donor cornea is one of the important factors responsible for endophthalmitis; hence all measures must be taken to reduce contamination of the tissue at donor screening, and strict asepsis must be maintained during tissue harvesting. Povidone-iodine is known to have antibacterial and antifungal action. Instillation of povidone-iodine 2.5% in the conjunctival cul-de-sac prior to retrieval of donor tissue significantly reduces microbial load of the donor cornea [19]. Contaminated tissue storage media are a potential source of infection. A change in the colour of the medium from pink to yellow indicates a change in pH and possible microbial contamination. Hence no donor tissue from such storage medium should be used for transplantation. The incidence of fungal endophthalmitis is less with organ-cultured corneas. This is mainly because of amphotericin B added to the organ culture media as well as microbiological screening which is routinely performed before using the tissue.
Management
Endophthalmitis is an infrequent but serious intraocular infection. A high level of suspicion helps, as timely intervention is the key to control the disease. Gram-positive organisms accounted for nearly half of all cases of endophthalmitis in one study; they exhibited 100% susceptibility to vancomycin, bacitracin and ampicillin, and only 75% of Gram-positive cocci were sensitive to cefazolin [9]. Gram-negative bacteria showed sensitivity to both ceftazidime and gentamicin [9]. Candida albicans is the most common infecting fungus. Topical antifungal medications are generally unstable and have poor corneal penetration [20]; according to the Infectious Diseases Society of America (IDSA) guidelines [21], intravenous voriconazole at a dosage of 3–4 mg/kg twice daily is safe and achieves excellent intravitreal levels for Candida endophthalmitis [22].
Unlike post-cataract surgery endophthalmitis, no study has shown a preferred route of antibiotic delivery in the treatment of post-penetrating keratoplasty endophthalmitis. According to the current microbiologic spectrum and susceptibilities, empiric antibiotic treatment should include vancomycin for Gram-positive bacteria and ceftazidime or amikacin for Gram-negative bacteria. Amphotericin B or voriconazole may be added in a case suspected of fungal endophthalmitis.
The mainstay of treatment of post-penetrating keratoplasty endophthalmitis is management of graft infection. Intravitreal antibiotics may have to be administered in a majority of cases. However, the integrity of the graft-host junction should be secured before intravitreal injection of drug. Pars plana vitrectomy using a temporary keratoplasty followed by repeat graft could be a viable option in fulminant cases.
Outcome
The outcome of post-penetrating keratoplasty endophthalmitis is dismal. As reported by Chen et al. [7], 5-year graft survival was only 27% after the development of endophthalmitis and the mean logMAR best corrected visual acuity in the surviving grafts was 1.13 (Snellen equivalent 20/269). In a review of Candida endophthalmitis after keratoplasty, 60% of cases resulted in visual acuity of 20/200 or worse [10].
Post-Refractive Surgery Endophthalmitis
Refractive error is the most common cause of ocular morbidity in the world. With improving technology and increased experience among ophthalmologists, there has been a tremendous increase in the number of people undergoing refractive surgeries. The realm of refractive surgery in vast majority includes incisional surgeries like radial keratectomy, ablative laser procedures like photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) and intraocular surgeries like phakic IOL implantation and refractive lens exchange. Since ablative laser procedures are primarily extraocular, the incidence of endophthalmitis in these cases is rather low with a few cases reported in literature. Intraocular surgeries like implantable collamer lens (ICL) have a considerable risk of endophthalmitis with a reported incidence of 1 in 6000, i.e. 0.0167% [23].
Risk Factors and Source
Patients at an increased risk of developing a persistent epithelial defect (e.g. corneal hypaesthesia, limbal stem cell deficiency and dry eye syndrome) are predisposed to the development of infection [24]. Patients should therefore be carefully assessed and counselled regarding these risks prior to surgery. The presence of corneal epithelial defect significantly increases the risk of infection. This is more in cases of PRK as compared to LASIK although small epithelial defects may be present with the latter as well. The use of bandage contact lens after PRK is a common practice. Although it may reduce pain and aid rapid re-epithelization, the risk of microbial keratitis is increased. Reduced corneal sensitivity which may persist for weeks after PRK may also be a contributing factor to infections [25]. The use of corticosteroids postoperatively further renders the eye susceptible to infections [26]. In post-LASIK eyes, the protection offered by the normal corneal epithelium and Bowman’s membrane is compromised, and the thinned cornea further increases the accessibility of the infective organism into the eye. There is also a higher chance of contamination of the interface with the patient’s own conjunctival secretions which is a potential source of infection. The use of microkeratome has an increased risk of infection compared to femtosecond laser-assisted LASIK surgeries. The incidence of fulminant infections is more in eyes with prior refractive surgeries, such as radial keratotomy (RK) before LASIK or PRK procedures [27–30].
Etiology
Endophthalmitis post-refractive surgery is a rare entity. Mulhern et al. [31] reported a case of Streptococcus pneumoniae endophthalmitis following an uneventful astigmatic myopic LASIK correction. A case of postsurgical endophthalmitis following PRK in a patient with a remote history of RK was reported by Karth et al. [30]; the causative organism was methicillin-resistant Staphylococcus aureus. In an anonymous online survey across 21 countries between January 1998 and December 2006, three cases of endophthalmitis were reported, and Staphylococcus epidermidis was cultured in two of them [23]. There have been reported cases of endophthalmitis following refractive lens procedures caused by Fusarium, Pseudomonas aeruginosa and Aspergillus [32–34]. There are also case reports of late-onset Mycobacterium gordonae endophthalmitis following anterior chamber phakic intraocular lens (PIOL) implantation for high myopia [35], Streptococcus mitis/oralis endophthalmitis after complicated iris-fixated PIOL implantation [36], methicillin-resistant Staphylococcus epidermidis endophthalmitis following uncomplicated posterior chamber PIOL implantation [37] and Rhizobium radiobacter endophthalmitis after posterior chamber PIOL implantation for myopia 25 months after the primary surgery [38].
Clinical Features
The onset of symptoms is classified as ‘early’, if it occurs within 7 days of refractive surgery, and ‘late’ if it occurs 10 days or more after the last surgical intervention. The most prominent symptom is sudden diminution of vision. The patients may present with associated pain, photophobia and discharge.
In cases of endophthalmitis following LASIK, slit lamp examination could reveal epithelial defect with surrounding infiltrates. Flap oedema is present in a majority of cases. Stromal abscess with severe anterior chamber reaction is seen in many cases (Figs. 16.3 and 16.4). Associated findings of epithelial ingrowth and flap separation may also be seen. Interface debris and infiltrates should be carefully looked for.
Fig. 16.3
Post-LASIK infection with stromal abscess with anterior chamber exudates
Fig. 16.4
(Left) Post-LASIK keratitis with endophthalmitis; (right) following therapeutic graft
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