Deep Anterior Lamellar Keratoplasty With Melles Technique for Granular Corneal Dystrophy

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Deep Anterior Lamellar Keratoplasty with Melles’ technique: Mid-term clinical outcome Alberto Villarrubia, MD1; Graciana Fuentes-Páez, MD2; Isabel Dapena, MD3; Elisa Palacín, MD1 PURPOSE: To report the mid-term clinical outcome of deep anterior lamellar keratoplasty (DALK), in a representative group of patients, some of them with low and some of them with high risk allograft rejection (relatively high-risk patient population). METHODS: In 50 eyes of 45 patients, a DALK was performed using the Melles technique. Fifteen eyes were not available for follow-up. Clinical outcome parameters included best-corrected visual acuity, astigmatic error, perforation rate and number of intra- and postoperative complications RESULTS: After contact lens fitting, 19 eyes (83%) reached a BCVA of ≥ 20/40 (≥ 0.5) and 10 eyes (44%) ≥ 20/25 (≥ 0.8). The mean change in refractive spherical equivalent was –4.8 ± 5.2 D (range +6.75 to –17.0 D) and in refractive astigmatism was 3.8 ± 2.0 D (range 0.0 to 8.0 D). An intraoperative micro-perforation of the host stromal bed occurred in 4/50 eyes (8%). In 12/35 eyes (34%) an epithelial defect persisting for longer than one week was observed. Eight (23%) «high-risk» developed deep stromal or interface vascularization, contact lens induced pannus with suture loosening, diffuse lamellar keratitis, an epithelial rejection line, and/or a recurrence of herpetic interstitial keratitis, all of which were managed by topical steroid treatment and/or systemic antiviral medication. CONCLUSIONS: DALK may be a feasible and relatively safe technique for treatment of relatively complicated anterior corneal pathology. In both low and high risk cases, DALK gives good clinical outcomes, and postoperative complications may be managed easily. KEY WORDS: Deep anterior lamellar keratoplasty, Melles’ technique, cornea transplant. J Emmetropia 2010; 1: 182-186 INTRODUCTION Deep anterior lamellar keratoplasty (DALK) refers to a surgical procedure in which the corneal stroma is replaced while keeping the host endothelium in situ, either with a thin layer of residual stroma or only the Descemet membrane (DM)1-3. Advantages of DALK over penetrating keratoplasty (PK) include faster visual

Submitted: 10/25/2010 Revised: 11/30/2010 Accepted: 12/8/2010 1 2 3

Instituto de Oftalmología La Arruzafa. Córdoba. Spain. Clínica TEKNON. Barcelona. Spain. NIIOS. Rotterdam. Netherlands.

The authors have no commercial or proprietary interest in any of the products or companies mentioned herein. Corresponding author: Alberto Villarrubia Cuadrado, MD. Instituto de Oftalmología La Arruzafa. Avda/ Arruzafa, Nº 9. 14012, Córdoba, Spain. Telephone: +34 957401040; Fax: +34 957401407; Email: [email protected]

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recovery, and a lower risk of intra- and postoperative complications, like secondary glaucoma or cataracts, allograft rejection, expulsive haemorrhage, and endophthalmitis. Furthermore, the ocular integrity may be better preserved allowing topical steroids to be tapered quicker and the endothelium cell density may be better preserved over time4,5. However, a possible disadvantage versus penetrating keratoplasty could be worse visual acuity due to the presence of an interface. Indications for DALK include all corneal pathologies involving central and deep corneal stroma. A disadvantage may be that DALK may be technically more difficult to perform6-7. Apart from the conventional ‘layer-by-layer dissection technique, several techniques are currently available, originally described by Sugita8, Anwar (Big Bubble)9 and Melles10,11. Both the Sugita technique (hydro-dissection up to Descemet membrane) and the Big Bubble technique (air dissection of Descemet membrane), may allow a near anatomical restoration of the cornea after the implantation of a «full-thickness» donor (anterior) cornea. A drawback of the latter procedures ISSN: 2171-4703

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and extended up to the limbus with dissection spatulas (2110 spatula set, DORC International, Zuidland, The Netherlands). A viscoadaptive viscoelastic was injected into the stromal pocket, to displace the posterior corneal layers toward the iris, so that the anterior corneal layers could be trephinated until viscoelastic was seen to escape from the trephination wound. Vannas scissors were used to cut residual stromal attachments, so that a 8.0 to 9.0 mm recipient bed was obtained. Then, a 0.25 mm oversized donor anterior corneal button, with its Descemet membrane carefully removed, was sutured into the host bed with double running 10-0 nylon sutures11. Postoperative medication included topical antibiotic as well as dexamethasone or flouroquinolone four times daily tapered over four months. Sutures were removed at six to twelve months after surgery. To evaluate the outcome of the DALK procedure, we documented the best spectacle corrected visual acuity (BSCVA) and/or best corrected visual acuity with a rigid gas permeable contact lens (CL-BCVA), mean refractive spherical equivalent (MRSE), refractive astigmatism (one month after complete suture removal) as well as a number of intra- and postoperative complications (i.e. perforation rate or delayed epithelisation, defined as the presence of an epithelial defect at 1 week after surgery).

may be that perforation into the anterior chamber is relatively frequent, and if so, the perforation tends to be large enough to require conversion to a PK. With the Melles’ spatula dissection technique, a thin layer of recipient stroma is left in situ. Although the perforation rate of this technique may be lower, a further main advantage may be that in the event of a perforation, the perforation site tends to be small, so that the procedure can be completed as a lamellar keratoplasty. Since 2002, we routinely performed DALK using the Melles’ technique, for all indications with stromal disease in the presence of healthy endothelium.10,11 In the current study, we evaluated the mid-term results of DALK in a group of 50 eyes. MATERIAL AND METHODS Fifty eyes of 45 patients with various anterior corneal disorders were selected consecutively for DALK between March 2002 and September 2008, and all of them were enrolled in our study; 35 patients were male and 10 female. Mean patient age was 39.51 ± 14.31 years (range 3-83 years). DALK surgeries were performed by one surgeon (AV) using the Melles’ technique, that allows for visualization of the dissection depth during the performance of a lamellar dissection (monitoring the «mirror-effect», «indentation-effect», and «Descemet folding effect»), using a scleral approach to reach the deep corneal layers10. After a complete air-fill of the anterior chamber (AC)11, a stromal pocket, 90-95% in corneal depth, was obtained

RESULTS Of the 50 DALK eyes, 15 eyes were lost to followup for reasons listed in Table 1. Complete follow-up

Table 1: Low and high graft risk rejection groups undergoing DALK with Melles’ technique Microperforation Delayed Second Intra-operative that did not epithelialization HSV DALK convertion to PK preclude to (Persistent reactivation / Interface Endothelial performed because of complete the Graft epithelial Epithelial infectious neo-vas- decompen- after initial Number macroperforation DALK procedure decentration defect) rejection keratitis cularization sation DALK Patient not available for follow-up

5*

Low risk allograft rejection Keratoconus Non vascularized Scar Post-LASIK ectasia Pellucid marginal degeneration

17 11 5 3

High risk allograft rejection Vascularized HSV scar Vascularized postinfectious scar Neurotrophic keratitis

6 2 1

Total

50

Boston Penetrating Keratokeratoplasty prosthesis performed performed after DALK after DALK

1 6*

1 1

3 3

1

3*

3 1 1

4 (3) 1 1

2/0 0/1

2

1 1 1*

* 15 eyes considered in the text «lost to follow up» (patients lost to follow-up in the first three months or eyes reconverted to other procedures in the first three months after DALK). JOURNAL OF EMMETROPIA - VOL 1, OCTOBER-DECEMBER

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was recorded for 35 eyes (mean 2.54 ± 1.6 years). Of the 35 eyes followed, 12 eyes had low visual potential (≤ 20/40; ≤ 0.5) due to pre-existing disorders unrelated to the corneal transplant.

Complications

In the group of 23 eyes with normal visual potential (35 with a completed follow up minus 12 with low potential visual acuity), a BSCVA of ≥ 20/40 (≥ 0.5) was obtained by 16 eyes (70%), and ≥ 20/25 (≥ 0.8) by 8 eyes (35%). After contact lens fitting, a BCVA of ≥ 20/40 (≥ 0.5) was reached by 19 eyes (83%), and ≥ 20/25 (≥ 0.8) by 10 eyes (44%). In this group of patients, the mean refractive spherical equivalent was 4.81 ± 5.24 (+6.75 to –17 D) and the mean refractive astigmatism was 3.84 ± 2.0 (0 to 8 D). Of the (23-19) four eyes that did not reach BCVA of ≥ 20/40 (≥ 0.5), two eyes had a final BSCVA of ≤ 20/200 (≤ 0.1). One eye developed an infectious keratitis apparently unrelated to the DALK surgery, and one eye had a decentred donor button. Two eyes with recurrent herpetic disease achieved a BSCVA of only 20/80 (0,25).

During DALK surgery, a macro perforation that did not allow going on with DALK procedure (i.e. Intraoperative conversion to PK procedure) occurred in 6/50 eyes (12%). A micro-perforation of the recipient stromal bed occurred in 4/50 eyes (8%) (Table 1). Immediately after surgery, delayed epithelisation of the donor button was observed in 12/35 eyes (34%). Of these eyes, three eyes developed a persistent epithelial defects requiring treatment with autologous serum. Eight «high-risk» corneas (Figures 1 and 2) were operated for post infectious scars (six of them due to herpetic keratitis) with deep stromal vascularization (Table 1). After DALK surgery, two eyes developed interface neovascularization, contact lens induced pannus and suture loosening, that was managed by highdose topical steroid treatment. A third eye developed a secondary diffuse lamellar keratitis that resolved after surgical irrigation of the donor-to-host interface. In three eyes with pellucid marginal degeneration an epithelial rejection line was seen at 3 to 6 months after surgery and that resolved with topical steroid treatment

Figures 1A and 1B. Pre- and postoperative image of deep anterior lamellar keratoplasty (DALK) in a «high-risk» cornea. Postoperative BSCVA at 12 months was 1,0.

Figures 2A and 2B. Pre- and postoperative image of deep anterior lamellar keratoplasty (DALK) in a «high-risk» cornea. Postoperative BSCVA at 12 months was 0,8.

Visual outcome

JOURNAL OF EMMETROPIA - VOL 1, OCTOBER-DECEMBER

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either Melles’ technique or the Big bubble technique, with up to 93% reaching ≥ 20/40 (≥ 0.5) and/or approximately 85% ≥ 20/25 (≥ 0.8). These differences may in part be explained by the heterogeneity in surgical indications among the studies. Since about one fourth of cases in our study may have been «high risk» eyes, a lower overall visual prognosis was to be anticipated than that after DALK for keratoconus alone. In recent years, several published studies reported that the visual outcome after DALK was at least be equal to penetrating keratoplasty18, whereas other studies reported better results after penetrating keratoplasty19. These conflicting reports may in part be explained by the use of different DALK techniques and differences in patient populations. Furthermore, a major confounding variable may be that surgeons tend to perform a DALK, but not a penetrating keratoplasty, in «high-risk» or complicated anterior corneal pathology. A retrospective review of the outcomes then becomes rather challenging, since excluding «the bad cases» would be scientifically inappropriate, although clinically justifiable. Incorporating «high-risk» cases in our study may therefore have complicated the comparison of the visual outcome among DALK studies, as well as with studies on penetrating keratoplasty. Further advantages of DALK over penetrating keratoplasty may relate to parameters that are clinically relevant but sometimes difficult to quantify. First, a major advantage of DALK may be that the postoperative refractive shift usually is «acceptable». In our study, 3.8 D of postoperative astigmatism after DALK compares with that reported by others8-9,12-17. Also, a mean spherical equivalent of –4.81 D may have been similar to that reported in foregoing studies8-9. Our study therefore confirms that DALK, on average, may induce less of an astigmatic and/or refractive shift than that after penetrating keratoplasty18-19. As a result, the residual refractive error after DALK can usually be corrected with a well-tolerated hard contact lens.

Figure 3. Slit lamp image of a cornea that developed an epithelial rejection line 3 months after deep anterior lamellar keratoplasty (DALK) for pellucid marginal degeneration.

without further squealae (Figure 3). A borderline endothelial decompensation, i.e. sub epithelial corneal oedema resolving over the day, was observed in one eye that had DALK surgery for a stromal scar after a corneal caustic burn with secondary iris atrophy, and corectopia. Recurrence of a herpetic interstitial keratitis episode was found in two eyes that could both be managed by topical steroids and systemic antiviral medication. DISCUSSION In our study, using Melles’ technique for DALK, a majority of eyes (83%) obtained a BCVA of ≥ 20/40 (≥ 0.5) and about half of the eyes reached ≥ 20/25 (≥ 0.8). These outcomes may compare to those reported by others, using the same technique, the «Sugita-technique», or the «Big-bubble technique» (Table 2)3,8-9,12-17. Some authors have reported better visual outcomes using Table 2: Comparision outcome of DALK in different series Study (Reference in text)

Amayen Anwar (3)

Sugita (8)

Tsubota (15)

El Danasoury (16)

Melles (11)

Caporossi (12)

Watson (13)

Nobel (14)

Villarrubia (current study)

Surgical Technique

Fluid

Fluid

Manual

Big Bubble

Melles

Melles

Melles

Melles

Melles

Surgical Indication

Keratoconus

Heterogeneous Keratoconus Keratoconus Heterogeneous Keratoconus Keratoconus Heterogeneous Heterogeneous

Perforation rate

8%

39%

6%

9%

% > 20/40 (0,5)

87,5%

62,8%

NR

% > 20/25 (0,8)

25%

NR

Postkeratoplasty astigmatism

2,54

NR

10%

11%

15%

8,8%

12%

83%

78%

87,5%

84,9%

70%

NR

16%

NR

32%

24,7%

35%

3,2

3,25

NR

1,63

3,31

3,84

2,6

NR: not referenced. JOURNAL OF EMMETROPIA - VOL 1, OCTOBER-DECEMBER

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Second, the risk of intraoperative complications may be lower with DALK than with penetrating keratoplasty, because it is essentially an «extra ocular» procedure. The risk of damaging the crystalline lens or any other intraocular structures, expulsive haemorrhage and/or endophthalmitis, may therefore be minimized. During surgery however, micro perforation have been reported to occur in 10-25% of cases, with either Sugita’s technique, Melles’ technique, or the Big bubble technique8-9,12-17. Our study confirms this finding with micro perforations in 8% of cases. When a spatula dissection technique is used, the micro perforation tends to be small, and when the anterior chamber can be maintained with a complete air-fill, the procedure can usually be finished as a lamellar corneal transplant. After surgery, a pseudo-anterior chamber may form, ie the presence of aqueous humour in the donor-to-host interface due to leakage of aqueous through the perforation site. In our experience, such pseudo-AC commonly resolves spontaneously, and if not, it can be managed by a secondary air-fill of the anterior chamber, to apposition the donor and host tissues17. Third, allograft rejection may be easier to manage and/or graft survival may be better after DALK than after penetrating keratoplasty20. An 8% epithelial and/or stromal rejection rate have been reported after DALK for keratoconus13,20. In our study, four cases (8%) presented with an epithelial rejection which resolved quickly after topical steroid treatment. Three rejections occurred in eyes operated for pellucid marginal degeneration that had 9.0 mm diameter grafts. The fourth rejection occurred in a high risk eye. In two eyes that had a DALK for a scar after herpes interstitial keratitis, recurrent herpes episodes were seen after antiviral medication was discontinued on the patient’s own initiative. In all of these cases, allograft rejection would probably have resulted in a more complicated clinical course if a penetrating keratoplasty had been performed. Since larger grafts may give better visual outcomes, long-term patient compliance to medication is limited, and vascularized and/or post infectious corneas may be prone to late allograft rejection, a DALK may be considered as the preferred treatment method in cases with a high risk of graft complication. In conclusion, the mid-term clinical outcome as analyzed in our study indicates that the Melles’ DALK technique is a safe and feasible technique in the management of anterior corneal pathology. Especially in a patient population with a relative high number of high risk cases, we feel that DALK may be the preferred method of treatment.

2. Benson WH, Goosey CB, Prager TC, Goosey JP. Visual improvement as a function of time after lamellar keratoplasty for keratoconus. Am J Ophthalmol 1993; 116: 207-211. 3. Amayem AF, Anwar M. Fluid lamellar keratoplasty in keratoconus. Ophthalmology 2000; 107: 76-80. 4. Wood TO. Lamellar transplants in keratoconus. Am J Ophthalmol 1977; 83: 543-545. 5. Morris E, Kirwan JF, Sujatha S, Rostron CK. Corneal endothelial specular microscopy following deep lamellar keratoplasty with lyophilized tissue. Eye 1998; 12: 619-622. 6. Hirano K, Sugita J, Kobayashi M. Separation of corneal stroma and Descemet’s membrane during deep lamellar keratoplasty. Cornea 2002; 21: 196-199. 7. Teichmann KD. Lamellar keratoplasty – a comeback? Middle East J Ophthalmol 1999; 7: 59-60. 8. Sugita J, Kondo J. Deep lamellar keratoplasty with complete removal of pathological stroma for vision improvement. Br J Ophthalmol 1997; 81: 184-188. 9. Anwar M, Teichmann KD. Big-bubble technique to bare Descemet’s membrane in anterior lamellar keratoplasty. J Cataract Refract Surg 2002; 28: 398-403. 10. Melles G, Rietveld F, Beekhuis WH, Binder PS. A technique to visualize corneal incision lamellar dissection depth during surgery. Cornea 1999; 18: 80-86. 11. Melles GRJ, Lander F, Rietveld FJR, et al. A new surgical technique for deep stromal, anterior lamellar keratoplasty. Br J Ophthalmol 1999; 83: 327-333. 12. Caporossi A, Simi C, Licignano R, et al. Air-guided manual deep lamellar keratoplasty. Eur J Ophthalmol 2004; 14: 55-58. 13. Watson SL, Ramsay A, Dart JKG, Bunce C, Craig E. Comparision of deep lamellar keratoplasty and penetrating keratoplasty in patients with keratoconus. Ophthalmology 2004; 111: 1676-1682. 14. Noble BA, Agrawal A, Collins C, Saldana M, Brogden PR, Zuberbuhler B. Deep anterior lamellar keratoplasty (DALK). Visual outcome and complications for a heterogeneous group of corneal pathologies. Cornea 2007; 26: 59-64. 15. Tsubota K, Kaido M, Monden Y, et al. A new surgical technique for deep lamellar keratoplasty with single running suture adjustment. Am J Ophthalmol 1998; 126: 1-8. 16. El-Danasoury MA. Deep lamellar keratoplasty for keratoconus: 1-year Results. J Refract Surg 2004; 20: S753 (Symposium Abstracts). 17. Villarrubia A, Pérez-Santonja JJ, Palacín E, Rodríguez Ausín P, Hidalgo A. Deep anterior lamellar keratoplasty in post-laser in situ keratomileusis keratectasia. J Cataract Refract Surg 2007; 33: 773-778. 18. Shimazaki J, Shimmura S, Ishioka M, Tsubota K. Randomized clinical trial of deep lamellar keratoplasty vs penetrating keratoplasty. Am J Ophthalmol 2002; 134: 159-165. 19. Olson R, Pingree M, Ridges R, Lundergan M, Alldredge C, Clinch T. Penetrating keratoplasty for keratoconus: a longterm review of results and complications. J Cataract Refract Surg 2000; 26: 987-991. 20. Watson SL, Tuft SJ, Dart JKG. Patterns of rejection after deep lamellar keratoplasty. Ophthalmology 2006; 113: 556-560.

REFERENCES 1. Anwar M, Teichmann K. Deep lamellar keratoplasty. Surgical techniques for anterior lamellar keratoplasty with and without baring of Descemet`s membrane. Cornea 2002; 21: 374-383. JOURNAL OF EMMETROPIA - VOL 1, OCTOBER-DECEMBER

First author: Alberto Villarrubia, MD Responsable de la Sección de Córnea y Cirugía Refractiva del Instituto de Oftalmología La Arruzafa. Córdoba. Spain

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