DALK in Complex Situations

Corneal Infections, Chemical Burns, and Others

Namrata Sharma, MD; Deepali Singhal, MD, DNB, FICO, FICO Cornea; Pranita Sahay, MD; and Prafulla Maharana, MD

Deep anterior lamellar keratoplasty (DALK) is a well-known surgical technique that involves excision of the pathological stroma until the Descemet’s membrane (DM), leaving the original corneal endothelium intact.¹ This has been described as the Descemetic DALK (D-DALK). If, however, around 90% of the stroma is removed leaving behind a layer of posterior stroma, it is termed as pre-Descemetic DALK (PD-DALK).¹

The major advantages as compared to penetrating keratoplasty (PK) include avoiding the complications associated with an open-sky surgery, a low-risk of graft rejection, less postoperative management, and optimal utilization of donor corneas in developing countries. All these advantages, especially the advantages of being a predominantly extraocular procedure, together with lack of endothelial rejection makes DALK a suitable procedure in difficult situations, like ocular surface diseases, infectious keratitis, and descmetocele.^1–3

DALK IN CORNEAL INFECTIONS

The mainstay of therapy of infective keratitis is medical management initially. Surgical management is required in instances of refractory cases, descemetocele, scleral extension, and corneal perforation.^4,5 To date, therapeutic PK has been the standard procedure for infective keratitis. However, it is associated with certain limitations, including high risk of graft failure because of recurrence (50% to 82%), endophthalmitis (ie, intraocular spread of infection during surgery), and a subsequent higher risk of graft rejection in subsequent optical grafts in these inflamed, often vascularized, high-risk eyes.6 DALK has been tried as a surgical option in infective keratitis (termed as therapeutic DALK [T-DALK]) for cases of bacterial, fungal, viral, Acanthamoeba as well as Microsporidia keratitis.^4,6–10

Indications

Infective keratitis involving the corneal stroma with sparing of the DM-endothelium complex and refractory to medical therapy is the main indication of T-DALK.

Contraindications

In the scenario of infective keratitis, DALK is contraindicated when there is full-thickness corneal involvement requiring PK, or in the presence of corneal perforation.

Advantages

The advantages of DALK over PK in case of infective keratitis include reduced risk of complications, such as endophthalmitis, endothelial graft rejection and subsequent failure, cataract, or glaucoma; reduced risk of complications associated with open-sky procedures; decreased requirement for prolonged use of steroids; and optimal utilization of donor corneas in developing countries. It helps healing by removing the infective focus, limiting the intraocular spread, and minimizing the risk of graft failure.

Preoperative Evaluation

A detailed ocular history is important, along with a meticulous slit lamp examination. Anterior and posterior segment examination should be completed along with measurement of intraocular pressure. Extent of stromal infiltration and the depth of involvement should be carefully noted. An anterior segment optical coherence tomography can also help in assessing the depth of stromal involvement. A detailed microbiological examination of corneal scraping is required to know the infective agent.

Surgical Technique

Various techniques have been described for DALK, such as the air- or viscoelastic-assisted techniques, Melles technique, hydrodelamination, big bubble and double bubble techniques, diamond knife–assisted manual dissection, and femtosecond-assisted DALK.¹ However, in cases of infective keratitis, the preferred techniques include big bubble DALK and manual layer-by-layer dissection.^4,6–10

The big bubble technique leads to complete baring of DM (D-DALK), whereas manual dissection retains some of the posterior stroma (PD-DALK). The big bubble technique is preferred in cases with normal peripheral cornea as well as relatively uninvolved posterior stromal layer. This is also preferred in cases of fungal and Acanthamoeba keratitis due to higher chances of retention of the infective organism in posterior stromal layers.4 Air injection should be avoided in cases with necrotic stroma, such as Pseudomonas keratitis.

Anesthesia

Informed consent for the surgery should be obtained. The surgery can be performed under local anesthesia, though general anesthesia may be preferred in children and uncooperative patients, as well as to avoid the risk of perforation of bare DM intraoperatively.

Host Bed Preparation

A modified form of the standard Anwar big bubble technique has been described in most clinical studies.^4,6–10 An 8.00- to 9.00-mm partial-thickness (60%) trephination with the Hanna corneal trephine (Moria) is performed. Manual anterior lamellar dissection of the anterior stroma is then done with a crescent blade (1.25 mm; Sharpoint) to a depth of approximately 50% of the corneal stroma. A 30-gauge needle attached to a 2-mL syringe and bent at 15° to 30° is advanced with bevel down into the paracentral corneal stroma. About 1 to 1.5 mL of sterilized air is injected into the posterior stroma until a big bubble is formed extending to the border of trephination. Residual stroma is then removed in quadrants, revealing bare DM. In cases with lack of big bubble formation, manual dissection is continued.

Donor Preparation

Full-thickness donor corneal tissues are used for transplantation. The donor cornea is punched from the endothelial side and is oversized by 0.25 mm. The donor DM and endothelium are stained with 0.06% trypan blue dye and then gently stripped using 0.12 mm non-toothed forceps or Merocel sponge (Beaver-Visitec International). This donor cornea is then sutured to the recipient with 16 interrupted 10-0 monofilament nylon sutures.

Viscoelastic-assisted DALK in descemetocele has been described by Sharma et al¹¹ in 12 cases of resolved microbial keratitis (Figure 10-1). All cases but 1 had significant improvement in visual acuity with clear grafts in 10 cases at last follow-up.

Postoperative Treatment

The postoperative medication consists of a topical antimicrobial agent tailored according to the causative organism.^3,4 In cases of bacterial infections, intensive, broad-spectrum antibiotic combinations are continued in the immediate postoperative period, together with systemic antibiotic cover, and gradually tapered if infection does not recur. Topical steroids for confirmed bacterial infections are usually initiated on postoperative day 3 or 4. For fungal infections, aggressive topical antifungal treatment in combination with oral fluconazole or voriconazole is given. Antifungal treatment is maintained over a prolonged period of up to several months after surgery. Topical steroids are usually withheld for at least 1 to 2 weeks after surgery. Topical cyclosporine (0.5%) can be used in the early postoperative period as a steroid-sparing agent and for its potential antifungal effect. For Acanthamoeba keratitis, patients are maintained on multiple medications, including combination of polyhexamethylbiguanide, chlorhexidine, propamidine isethionate, and hexamidine, with or without topical steroids, for several weeks to months after surgery, with gradual tapering.3,4

Complications

The specific complications of DALK in infectious keratitis are included in the following sections.

The most important intraoperative complication of DALK is DM perforation.3 Its incidence ranges between 4% and 20%, and this can occur at any step of surgery. A small perforation can be managed by intracameral injection of air and careful stromal dissection, while a large perforation requires conversion to PK. Anshu et al⁴ reported intraoperative microperforation in 15.3% of cases but none required conversion to PK. Gao et al¹² noted perforation in 8.7% of cases of deep fungal keratitis. No intraoperative complication was seen in T-DALK done in a case of post-LASIK mycobacterial keratitis.¹² Sarnicola et al⁸ reported 1 case (out of 11) with intraoperative microperforation during PD-DALK.

Pseudo Anterior Chamber

Anshu et al⁴ reported postoperative DM detachment in 15.3% of cases that spontaneously resolved in most of the cases, and 1 was managed with intracameral air injection. Gao et al¹² noted perforation and double anterior chamber in 13% of cases of deep fungal keratitis.

Endophthalmitis

There was no case of T-DALK with postoperative endophthalmitis noted by Anshu et al⁴ as compared to PK, which had an incidence of 5% to 10%.

Graft Rejection

Anshu et al⁴ reported 10% to 15% incidence of graft rejection in PK group as compared to none in T-DALK group. Gao et al¹² noted stromal graft rejection in only 1 case (4.3%) of deep fungal keratitis during the first 3 months after surgery. No postoperative complication was seen in T-DALK done in a case of post-LASIK mycobacterial keratitis as well as in Acanthamoeba keratitis.^6,8,13

Graft Failure

Late graft failure is reported to be in 1/26 cases in T-DALK as compared to 8/100 cases in PK group.⁴

Outcomes

Therapeutic Outcome

Anshu et al⁴ reported recurrence in 4 patients (15.3%) in the T-DALK group compared with 12 (12%) in the PK group. The primary cause for eyes that developed a recurrence in the T-DALK group was bacterial (n = 2), fungal (n = 1), and Acanthamoeba (n = 1); all underwent surgery using the manual dissection technique. No recurrence of infection occurred in the T-DALK cases with total stromal removal. The T-DALK group also showed a trend toward better graft survival as compared to PK group (90% vs 78.4%).⁴ Gao et al¹² reported a successful outcome of T-DALK in cases of deep fungal keratitis (4/5 of stromal involvement) with a recurrence in only 8.7% cases. No evidence of recurrence was seen in T-DALK done in a case of post-LASIK mycobacterial keratitis.13

Early T-DALK (within 30 to 60 days) has been considered a new approach to manage refractory/nonresponsive cases of Acanthamoeba keratitis. No episode of recurrence or failure was noted in these cases.^6,8 T-DALK has also been used successfully with no signs of recurrence or rejection for the treatment of microsporidial stromal keratitis.¹⁰

Visual Outcome

Anshu et al⁴ reported a similar visual outcome in T-DALK and PK groups with a trend toward a better outcome in the DALK group. Gao et al¹² noted a significant improvement in visual acuity after T-DALK in deep fungal keratitis. A good visual outcome with an improvement from counting fingers to 20/50 was seen in a case of post-LASIK mycobacterial keratitis following T-DALK.¹³ Significant improvement in best-corrected visual acuity (BCVA) was noted in cases of non-responsive Acanthamoeba keratitis post–T-DALK.^6,8

DALK IN HERPETIC STROMAL KERATITIS

DALK has been evaluated in cases of active herpetic stromal keratitis (HSK), as well as quiescent and refractory cases.^9,14 It is a well-known fact that HSK can remain latent in the cornea leading to reactivation and increased risk of recurrence. PK is often required to eliminate most of the latent virus and thereby reduce the chances of recurrence. A recurrence rate of 25% in the first year and 44% in the second year has been reported with PK in HSK. The primary allograft rejection rate was 29% in the first year and 46% in the second.¹⁵ In addition, the risk of graft failure in patients who underwent PK for HSK was higher than average, possibly due to the associated endothelial dysfunction.^16,17 Considering the various advantages of DALK over PK, it seems to be a safe and promising procedure for HSK, with a favorable visual outcome, graft survival rate, and lower endothelial cell loss.

Oral acyclovir prophylaxis started at least 1 month before surgery until at least 1 year after surgery plays an important role in reducing the rate of recurrence and rejection.¹⁸ Various studies have shown encouraging outcomes with DALK as compared to PK in herpes simplex virus–related corneal scarring.^18–20 Awan et al¹⁹ reported a 3-year graft survival rate of 83%, with a recurrence rate of 5%, and rejection rate of 33%, showing a better outcome as compared to PK. DALK using glycerin-preserved cornea has also shown to be an effective and safe therapy in refractory HSK (ie, HSK that recurred perennially for at least 3 years, with a shorter and shorter onset interval, exacerbated yearly with a poorly therapeutic effect).¹⁴ However, a single study has evaluated the role of DALK in active HSK after amniotic membrane transplant and intravenous acyclovir.⁹ They showed a graft survival rate of 86% with a significant improvement in vision and a recurrence of 18% of cases with active disease. Stromal rejection was seen in 2.3% cases only.⁹

The ocular surface, including both the corneal and conjunctival epithelium, is severely compromised following chemical injury. Limbal stem cells, which are the source for corneal epithelial cell regeneration, are also damaged. As a consequence, there is conjunctivalization, chronic inflammation, vascularization, persistent epithelial defects, and scarring of the cornea.21 This results in symptoms of ocular discomfort and diminution of vision. Dense vascularization of the cornea predisposes to a high risk of graft rejection when conventional full-thickness keratoplasty is performed for these cases. Allogenic graft rejection rate as high as 57.7% has been reported in literature post-PK for chemical burn.²² Thus, lamellar keratoplasty can improve long-term visual outcome in these cases by retaining the host endothelium and reducing the risk of immunologic endothelial graft rejection.

Surgical Technique

The major surgical challenge when performing DALK in these cases is the presence of corneal thinning, superficial vascularization of cornea leading to intra- and postoperative bleeding, and poor visibility due to the presence of corneal haze. Taking into consideration these factors, we recommend PD-DALK with a layer-bylayer manual dissection technique. An initial partial-thickness corneal trephination is done with a 7.7- or 8-mm corneal trephine to 75% corneal depth (Figure 10-2A). Lamellar dissection is then performed with the aid of a crescent blade while lifting the stromal tissue with the help of forceps (Figures 10-2B and 10-2C). At this step, it is important to maintain the plane of dissection. After removing this layer, a second layer of dissection is initiated to remove as much stromal fibers as possible without compromising the DM. The dissection is continued until at least 95% of the stromal fibers are removed. The edges are dissected with the help of fine Vannas scissors (Figures 10-2D through 10-2G). After completing lamellar dissection of the host bed, the donor tissue is prepared by peeling off the DM-endothelium complex. Donor tissue trephination is done with 0.5 mm oversized trephine. This is then placed over the host bed and sutured with 16 interrupted 10-0 monofilament nylon sutures (Figures 102H and 10-2I). Care should be taken to avoid passage of full-thickness sutures.

A Successful DALK in cases of chemical injury usually results in excellent outcome (Figures 10-3 and 10-4).

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